Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review)
- Authors:
- Yun-Fan Li
- Shuai Su
- Yu Luo
- Chengcheng Wei
- Jingke He
- Liang-Dong Song
- Kun Han
- Jue Wang
- Xiangzhi Gan
- De-Lin Wang
-
Affiliations: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China - Published online on: July 4, 2025 https://doi.org/10.3892/or.2025.8942
- Article Number: 109
-
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
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 |
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|
Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2022. CA Cancer J Clin. 72:7–33. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Feldman BJ and Feldman D: The development of androgen-independent prostate cancer. Nat Rev Cancer. 1:34–45. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, et al: Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 371:424–433. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, et al: Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 364:1995–2005. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Davies AH, Beltran H and Zoubeidi A: Cellular plasticity and the neuroendocrine phenotype in prostate cancer. Nat Rev Urol. 15:271–286. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Yamada Y and Beltran H: Clinical and biological features of neuroendocrine prostate cancer. Curr Oncol Rep. 23:152021. View Article : Google Scholar : PubMed/NCBI | |
|
Zaffuto E, Pompe R, Zanaty M, Bondarenko HD, Leyh-Bannurah SR, Moschini M, Dell'Oglio P, Gandaglia G, Fossati N, Stabile A, et al: Contemporary incidence and cancer control outcomes of primary neuroend ocrine prostate cancer: A SEER database analysis. Clin Genitourin Cancer. 15:e793–e800. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Varga J and Greten FR: Cell plasticity in epithelial homeostasis and tumorigenesis. Nat Cell Biol. 19:1133–1141. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y and Wang Y, Ci X, Choi SYC, Crea F, Lin D and Wang Y: Molecular events in neuroendocrine prostate cancer development. Nat Rev Urol. 18:581–596. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Garabedian EM, Humphrey PA and Gordon JI: A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. Proc Natl Acad Sci USA. 95:15382–15387. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Merkens L, Sailer V, Lessel D, Janzen E, Greimeier S, Kirfel J, Perner S, Pantel K, Werner S and von Amsberg G: Aggressive variants of prostate cancer: Underlying mechanisms of neuroendocrine transdifferentiation. J Exp Clin Cancer Res. 41:462022. View Article : Google Scholar : PubMed/NCBI | |
|
Varma M, Lee MW, Tamboli P, Zarbo RJ, Jimenez RE, Salles PGO and Amin MB: Morphologic criteria for the diagnosis of prostatic adenocarcinoma in needle biopsy specimens. A study of 250 consecutive cases in a routine surgical pathology practice. Arch Pathol Lab Med. 126:554–561. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Epstein JI, Amin MB, Beltran H, Lotan TL, Mosquera JM, Reuter VE, Robinson BD, Troncoso P and Rubin MA: Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol. 38:756–767. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Spetsieris N, Boukovala M, Patsakis G, Alafis I and Efstathiou E: Neuroendocrine and aggressive-variant prostate cancer. Cancers. 12:37922014. View Article : Google Scholar | |
|
Weinstein MH, Partin AW, Veltri RW and Epstein JI: Neuroendocrine differentiation in prostate cancer: Enhanced prediction of progression after radical prostatectomy. Hum Pathol. 27:683–687. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Theodorescu D, Broder SR, Boyd JC, Mills SE and Frierson HF Jr: Cathepsin D and chromogranin A as predictors of long term disease specific survival after radical prostatectomy for localized carcinoma of the prostate. Cancer. 80:2109–2119. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Berruti A, Mosca A, Tucci M, Terrone C, Torta M, Tarabuzzi R, Russo L, Cracco C, Bollito E, Scarpa RM, et al: Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease. Endocr Relat Cancer. 12:109–117. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Bostwick DG, Qian J, Pacelli A, Zincke H, Blute M, Bergstralh EJ, Slezak JM and Cheng L: Neuroendocrine expression in node positive prostate cancer: Correlation with systemic progression and patient survival. J Urol. 168:1204–1211. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Conteduca V, Oromendia C, Eng KW, Bareja R, Sigouros M, Molina A, Faltas BM, Sboner A, Mosquera JM, Elemento O, et al: Clinical features of neuroendocrine prostate cancer. Eur J Cancer. 121:7–18. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Wang HT, Yao YH, Li BG, Tang Y, Chang JW and Zhang J: Neuroendocrine Prostate Cancer (NEPC) progressing from conventional pr ostatic adenocarcinoma: Factors associated with time to development of NEPC and survival from NEPC diagnosis-a systematic review and pooled analysis. J Clin Oncol. 32:3383–3390. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Montanari M, Rossetti S, Cavaliere C, D'Aniello C, Malzone MG, Vanacore D, Di Franco R, La Mantia E, Iovane G, Piscitelli R, et al: Epithelial-mesenchymal transition in prostate cancer: An overview. Oncotarget. 8:35376–35389. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Kalluri R and Neilson EG: Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest. 112:1776–1784. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Williams ED, Gao D, Redfern A and Thompson EW: Controversies around epithelial-mesenchymal plasticity in cancer metastasis. Nat Rev Cancer. 19:716–732. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Tiwari R, Manzar N and Ateeq B: Dynamics of cellular plasticity in prostate cancer progression. Front Mol Biosci. 7:1302020. View Article : Google Scholar : PubMed/NCBI | |
|
Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Bakir B, Chiarella AM, Pitarresi JR and Rustgi AK: EMT, MET, plasticity, and tumor metastasis. Trends Cell Biol. 30:764–776. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Liu YN, Chen WY, Yeh HL, Chen WH, Jiang KC, Li HR, Dung PVT, Chen ZQ, Lee WJ, Hsiao M, et al: MCTP1 increases the malignancy of androgen-deprived prostate cancer cells by inducing neuroendocrine differentiation and EMT. Sci Signal. 17:eadc91422024. View Article : Google Scholar : PubMed/NCBI | |
|
Conteduca V, Aieta M, Amadori D and De Giorgi U: Neuroendocrine differentiation in prostate cancer: Current and emerging therapy strategies. Crit Rev Oncol Hematol. 92:11–24. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 74:229–263. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Capp JP: Cancer stem cells: From historical roots to a new perspective. J Oncol. 2019:51892322019. View Article : Google Scholar : PubMed/NCBI | |
|
Phi LTH, Sari IN, Yang YG, Lee SH, Jun N, Kim KS, Lee YK and Kwon HY: Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int. 2018:54169232018. View Article : Google Scholar : PubMed/NCBI | |
|
Ayob AZ and Ramasamy TS: Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 25:202018. View Article : Google Scholar : PubMed/NCBI | |
|
Nguyen LV, Vanner R, Dirks P and Eaves CJ: Cancer stem cells: An evolving concept. Nat Rev Cancer. 12:133–143. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Pekovic V and Hutchison CJ: Adult stem cell maintenance and tissue regeneration in the ageing context: The role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. J Anat. 213:5–25. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Ojo D, Lin X, Wong N, Gu Y and Tang D: Prostate cancer stem-like cells contribute to the development of castration-resistant prostate cancer. Cancers (Basel). 7:2290–2308. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Brown TJ and James V: The role of extracellular vesicles in the development of a cancer stem cell microenvironment niche and potential therapeutic targets: A systematic review. Cancers (Basel). 13:24352021. View Article : Google Scholar : PubMed/NCBI | |
|
Plaks V, Kong N and Werb Z: The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 16:225–238. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Castellón EA, Indo S and Contreras HR: Cancer Stemness/epithelial-mesenchymal transition axis influences metastasis and castration resistance in prostate cancer: Potential therapeutic target. Int J Mol Sci. 23:149172022. View Article : Google Scholar : PubMed/NCBI | |
|
Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauß A, Blaudszun AR, Yevsa T, Fricke S and Kossatz-Boehlert U: Cancer stem cells-origins and biomarkers: Perspectives for targeted personalized therapies. Front Immunol. 11:12802020. View Article : Google Scholar : PubMed/NCBI | |
|
Xin L, Lawson DA and Witte ON: The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc Natl Acad Sci USA. 102:6942–6947. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Germann M, Wetterwald A, Guzmán-Ramirez N, van der Pluijm G, Culig Z, Cecchini MG, Williams ED and Thalmann GN: Stem-like cells with luminal progenitor phenotype survive castration in human prostate cancer. Stem Cells. 30:1076–1086. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ma F, Chen D, Chen F, Chi Y and Han Z, Feng X, Li X and Han Z: Human umbilical cord mesenchymal stem cells promote breast cancer metastasis by Interleukin-8- and Interleukin-6-Dependent Induction of CD44(+)/CD24(−) cells. Cell Transplant. 24:2585–2599. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Ji Y, Liu B, Chen L, Li A, Shen K, Su R, Zhang W, Zhu Y, Wang Q and Xue W: Repurposing ketotifen as a therapeutic strategy for neuroendocrine prostate cancer by targeting the IL-6/STAT3 pathway. Cell Oncol (Dordr). 46:1445–1456. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Kopczyńska E: Role of microRNAs in the resistance of prostate cancer to docetaxel and paclitaxel. Contemp Oncol (Pozn). 19:423–427. 2015.PubMed/NCBI | |
|
Verma P, Shukla N, Kumari S, Ansari MS, Gautam NK and Patel GK: Cancer stem cell in prostate cancer progression, metastasis and therapy resistance. Biochim Biophys Acta Rev Cancer. 1878:1888872023. View Article : Google Scholar : PubMed/NCBI | |
|
Castillo V, Valenzuela R, Huidobro C, Contreras HR and Castellon EA: Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer. Int J Oncol. 45:985–994. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Biserova K, Jakovlevs A, Uljanovs R and Strumfa I: Cancer stem cells: Significance in origin, pathogenesis and treatment of glioblastoma. Cells. 10:6212021. View Article : Google Scholar : PubMed/NCBI | |
|
Garcia-Mayea Y, Mir C, Masson F, Paciucci R and ME LL: Insights into new mechanisms and models of cancer stem cell multidrug resistance. Semin Cancer Biol. 60:166–180. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Satar NA, Fakiruddin KS, Lim MN, Mok PL, Zakaria N, Fakharuzi NA, Abd Rahman AZ, Zakaria Z, Yahaya BH and Baharuddin P: Novel triple-positive markers identified in human non-small cell lung cancer cell line with chemotherapy-resistant and putative cancer stem cell characteristics. Oncol Rep. 40:669–681. 2018.PubMed/NCBI | |
|
Duran GE, Wang YC, Francisco EB, Rose JC, Martinez FJ, Coller J, Brassard D, Vrignaud P and Sikic BI: Mechanisms of resistance to cabazitaxel. Mol Cancer Ther. 14:193–201. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Schreiber RD, Old LJ and Smyth MJ: Cancer immunoediting: Integrating immunity's roles in cancer suppression and promotion. Science. 331:1565–1570. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang D, Sun B, Zhao X, Ma Y, Ji R, Gu Q, Dong X, Li J, Liu F, Jia X, et al: Twist1 expression induced by sunitinib accelerates tumor cell vasculogenic mimicry by increasing the population of CD133+ cells in triple-negative breast cancer. Mol Cancer. 13:2072014. View Article : Google Scholar : PubMed/NCBI | |
|
Liu B, Li L, Yang G, Geng C, Luo Y, Wu W, Manyam GC, Korentzelos D, Park S, Tang Z, et al: PARP inhibition suppresses GR-MYCN-CDK5-RB1-E2F1 signaling and neuroendocrine differentiation in castration-resistant prostate cancer. Clin Cancer Res. 25:6839–6851. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Zhao Y, An Z and Li W: Molecular links between angiogenesis and neuroendocrine phenotypes in prostate cancer progression. Front Oncol. 9:14912020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Zheng D, Zhou T, Song H, Hulsurkar M, Su N, Liu Y, Wang Z, Shao L, Ittmann M, et al: Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers. Nat Commun. 9:40802018. View Article : Google Scholar : PubMed/NCBI | |
|
Ci X, Hao J, Dong X, Choi SY, Xue H, Wu R, Qu S, Gout PW, Zhang F, Haegert AM, et al: Heterochromatin protein 1α mediates development and aggressiveness of neuroendocrine prostate cancer. Cancer Res. 78:2691–2704. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chang PC, Wang TY, Chang YT, Chu CY, Lee CL, Hsu HW, Zhou TA, Wu Z, Kim RH, Desai SJ, et al: Autophagy pathway is required for IL-6 induced neuroendocrine differen tiation and chemoresistance of prostate cancer LNCaP cells. PLoS One. 9:e885562014. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu Y, Liu C, Cui Y, Nadiminty N, Lou W and Gao AC: Interleukin-6 induces neuroendocrine differentiation (NED) through sup pression of RE-1 silencing transcription factor (REST). Prostate. 74:1086–1094. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Fang D and Kitamura H: Cancer stem cells and epithelial-mesenchymal transition in urothelial carcinoma: Possible pathways and potential therapeutic approaches. Int J Urol. 25:7–17. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Hiraga T, Ito S and Nakamura H: EpCAM expression in breast cancer cells is associated with enhanced bone metastasis formation. Int J Cancer. 138:1698–1708. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Rycaj K, Li H, Zhou J, Chen X and Tang DG: Cellular determinants and microenvironmental regulation of prostate cancer metastasis. Semin Cancer Biol. 44:83–97. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Jeon HM and Lee J: MET: Roles in epithelial-mesenchymal transition and cancer stemness. Ann Transl Med. 5:52017. View Article : Google Scholar : PubMed/NCBI | |
|
Ruppender NS, Morrissey C, Lange PH and Vessella RL: Dormancy in solid tumors: Implications for prostate cancer. Cancer Metastasis Rev. 32:501–509. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Li H and Tang DG: Prostate cancer stem cells and their potential roles in metastasis. J Surg Oncol. 103:558–562. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Celià-Terrassa T and Kang Y: Metastatic niche functions and therapeutic opportunities. Nat Cell Biol. 20:868–877. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, Kim JK, Patel LR, Ying C, Ziegler AM, et al: Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. 121:1298–1312. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Kim JK, Jung Y, Wang J, Joseph J, Mishra A, Hill EE, Krebsbach PH, Pienta KJ, Shiozawa Y and Taichman RS: TBK1 regulates prostate cancer dormancy through mTOR inhibition. Neoplasia. 15:1064–1074. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Correnti M and Raggi C: Stem-like plasticity and heterogeneity of circulating tumor cells: Current status and prospect challenges in liver cancer. Oncotarget. 8:7094–7115. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Han H, Wang Y, Curto J, Gurrapu S, Laudato S, Rumandla A, Chakraborty G, Wang X, Chen H, Jiang Y, et al: Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis. Cell Rep. 39:1105952022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H and Unternaehrer JJ: Epithelial-mesenchymal transition and cancer stem cells: At the crossroads of differentiation and dedifferentiation. Dev Dyn. 248:10–20. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Li P, Wang J, Chu M, Zhang K, Yang R and Gao WQ: Zeb1 promotes androgen independence of prostate cancer via induction of stem cell-like properties. Exp Biol Med (Maywood). 239:813–822. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Tsai YC, Chen WY, Abou-Kheir W, Zeng T, Yin JJ, Bahmad H, Lee YC and Liu YN: Androgen deprivation therapy-induced epithelial-mesenchymal transition of prostate cancer through downregulating SPDEF and activating CCL2. Biochim Biophys Acta Mol Basis Dis. 1864:1717–1727. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Sun Y, Wang BE, Leong KG, Yue P, Li L, Jhunjhunwala S, Chen D, Seo K, Modrusan Z, Gao WQ, et al: Androgen deprivation causes epithelial-mesenchymal transition in the prostate: Implications for androgen-deprivation therapy. Cancer Res. 72:527–536. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Tang Y, Hamburger AW, Wang L, Khan MA and Hussain A: Androgen deprivation and stem cell markers in prostate cancers. Int J Clin Exp Pathol. 3:128–138. 2009.PubMed/NCBI | |
|
Qin J, Liu X, Laffin B, Chen X, Choy G, Jeter CR, Calhoun-Davis T, Li H, Palapattu GS, Pang S, et al: The PSA(−/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell. 10:556–569. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Rybak AP, He L, Kapoor A, Cutz JC and Tang D: Characterization of sphere-propagating cells with stem-like properties from DU145 prostate cancer cells. Biochim Biophys Acta. 1813:683–694. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Han M, Li F, Zhang Y, Dai P, He J, Li Y, Zhu Y, Zheng J, Huang H, Bai F, et al: FOXA2 drives lineage plasticity and KIT pathway activation in neuroend ocrine prostate cancer. Cancer Cell. 40:1306–1323.e8. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Nouruzi S, Ganguli D, Tabrizian N, Kobelev M, Sivak O, Namekawa T, Thaper D, Baca SC, Freedman ML, Aguda A, et al: ASCL1 activates neuronal stem cell-like lineage programming through re modeling of the chromatin landscape in prostate cancer. Natu Commun. 13:22822022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Wang T, Hong D, Dong B, Wang Y, Huang H, Zhang W, Lian B, Ji B, Shi H, et al: Single-cell transcriptional regulation and genetic evolution of neuroe ndocrine prostate cancer. iScience. 25:1045762022. View Article : Google Scholar : PubMed/NCBI | |
|
Singh N, Ramnarine VR, Song JH, Pandey R, Padi SKR, Nouri M, Olive V, Kobelev M, Okumura K, McCarthy D, et al: The long noncoding RNA H19 regulates tumor plasticity in neuroendocrin e prostate cancer. Nat Commun. 12:73492021. View Article : Google Scholar : PubMed/NCBI | |
|
Long Z, Deng L, Li C, He Q, He Y, Hu X, Cai Y and Gan Y: Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer. Cell Death Dis. 12:462021. View Article : Google Scholar : PubMed/NCBI | |
|
Luo J, Wang K, Yeh S, Sun Y, Liang L, Xiao Y, Xu W, Niu Y, Cheng L, Maity SN, et al: LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling. Nat Commun. 10:25712019. View Article : Google Scholar : PubMed/NCBI | |
|
Kaarijärvi R, Kaljunen H, Nappi L, Fazli L, Kung SHY, Hartikainen JM, Paakinaho V, Capra J, Rilla K, Malinen M, et al: DPYSL5 is highly expressed in treatment-induced neuroendocrine prostate cancer and promotes lineage plasticity via EZH2/PRC2. Commun Biol. 7:1082024. View Article : Google Scholar : PubMed/NCBI | |
|
Shui X, Ren X, Xu R, Xie Q, Hu Y, Qin J, Meng H, Zhang C, Zhao J and Shi C: Monoamine oxidase A drives neuroendocrine differentiation in prostate cancer. Biochem Biophys Res Commun. 606:135–141. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Chen R, Li Y, Buttyan R and Dong X: Implications of PI3K/AKT inhibition on REST protein stability and neur oendocrine phenotype acquisition in prostate cancer cells. Oncotarget. 8:84863–84876. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Bishop JL, Thaper D, Vahid S, Davies A, Ketola K, Kuruma H, Jama R, Nip KM, Angeles A, Johnson F, et al: The master neural transcription factor BRN2 is an androgen receptor-suppressed driver of neuroendocrine differentiation in prostate cancer. Cancer Discov. 7:54–71. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Nie J, Zhang P, Liang C, Yu Y and Wang X: ASCL1-mediated ferroptosis resistance enhances the progress of castrat ion-resistant prostate cancer to neurosecretory prostate cancer. Free Radic Biol Med. 205:318–331. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Akamatsu S, Wyatt AW, Lin D, Lysakowski S, Zhang F, Kim S, Tse C, Wang K, Mo F, Haegert A, et al: The placental gene PEG10 promotes progression of neuroendocrine prosta te cancer. Cell reports. 12:922–936. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Deep G, Jain AK, Ramteke A, Ting H, Vijendra KC, Gangar SC, Agarwal C and Agarwal R: SNAI1 is critical for the aggressiveness of prostate cancer cells with low E-cadherin. Mol Cancer. 13:372014. View Article : Google Scholar : PubMed/NCBI | |
|
Bae KM, Su Z, Frye C, McClellan S, Allan RW, Andrejewski JT, Kelley V, Jorgensen M, Steindler DA, Vieweg J, et al: Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells. J Urol. 183:2045–2053. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Bae KM, Parker NN, Dai Y, Vieweg J and Siemann DW: E-cadherin plasticity in prostate cancer stem cell invasion. Am J Cancer Res. 1:71–84. 2011.PubMed/NCBI | |
|
Orellana-Serradell O, Herrera D, Castellon EA and Contreras HR: The transcription factor ZEB1 promotes an aggressive phenotype in prostate cancer cell lines. Asian J Androl. 20:294–299. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG, Reinhardt F, D'Alessio AC, Young RA and Weinberg RA: Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell. 154:61–74. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kong D, Banerjee S, Ahmad A, Li Y, Wang Z, Sethi S and Sarkar FH: Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One. 5:e124452010. View Article : Google Scholar : PubMed/NCBI | |
|
Onder TT, Gupta PB, Mani SA, Yang J, Lander ES and Weinberg RA: Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 68:3645–3654. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Akunuru S, James Zhai Q and Zheng Y: Non-small cell lung cancer stem/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity. Cell Death Dis. 3:e3522012. View Article : Google Scholar : PubMed/NCBI | |
|
Soundararajan R, Paranjape AN, Maity S, Aparicio A and Mani SA: EMT, stemness and tumor plasticity in aggressive variant neuroendocrine prostate cancers. Biochim Biophys Acta Rev Cancer. 1870:229–238. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
McKeithen D, Graham T, Chung LW and Odero-Marah V: Snail transcription factor regulates neuroendocrine differentiation in LNCaP prostate cancer cells. Prostate. 70:982–992. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Dicken H, Hensley PJ and Kyprianou N: Prostate tumor neuroendocrine differentiation via EMT: The road less traveled. Asian J Urol. 6:82–90. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, et al: Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 122:947–956. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Sarkar A and Hochedlinger K: The sox family of transcription factors: Versatile regulators of stem and progenitor cell fate. Cell Stem Cell. 12:15–30. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang S and Cui W: Sox2, a key factor in the regulation of pluripotency and neural differ entiation. World J Stem Cells. 6:305–311. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Metz EP, Wilder PJ, Dong J, Datta K and Rizzino A: Elevating SOX2 in prostate tumor cells upregulates expression of neuro endocrine genes, but does not reduce the inhibitory effects of enzalut amide. J Cell Physiol. 235:3731–3740. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Kwon OJ, Zhang L, Jia D and Xin L: Sox2 is necessary for androgen ablation-induced neuroendocrine differe ntiation from Pten null Sca-1+ prostate luminal cells. Oncogene. 40:203–214. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Tiwari R, Manzar N, Bhatia V, Yadav A, Nengroo MA, Datta D, Carskadon S, Gupta N, Sigouros M, Khani F, et al: Androgen deprivation upregulates SPINK1 expression and potentiates cel lular plasticity in prostate cancer. Nature Commun. 11:3842020. View Article : Google Scholar : PubMed/NCBI | |
|
Li H, Wang L, Li Z, Geng X, Li M, Tang Q, Wu C and Lu Z: SOX2 has dual functions as a regulator in the progression of neuroendo crine prostate cancer. Lab Invest. 100:570–582. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Kregel S, Kiriluk KJ, Rosen AM, Cai Y, Reyes EE, Otto KB, Tom W, Paner GP, Szmulewitz RZ and Vander Griend DJ: Sox2 is an androgen receptor-repressed gene that promotes castration-r esistant prostate cancer. PLoS One. 8:e537012013. View Article : Google Scholar : PubMed/NCBI | |
|
Kareta MS, Gorges LL, Hafeez S, Benayoun BA, Marro S, Zmoos AF, Cecchini MJ, Spacek D, Batista LF, O'Brien M, et al: Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis. Cell Stem Cell. 16:39–50. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Lovnicki J, Gan Y, Feng T, Li Y, Xie N, Ho CH, Lee AR, Chen X, Nappi L, Han B, et al: LIN28B promotes the development of neuroendocrine prostate cancer. J Clin Invest. 130:5338–5348. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Yasumizu Y, Rajabi H, Jin C, Hata T, Pitroda S, Long MD, Hagiwara M, Li W, Hu Q, Liu S, et al: MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer. Nat Commun. 11:3382020. View Article : Google Scholar : PubMed/NCBI | |
|
Patel GK, Dutta S, Syed MM, Ramachandran S, Sharma M, Rajamanickam V, Ganapathy V, DeGraff DJ, Pruitt K, Tripathi M, et al: TBX2 Drives Neuroendocrine Prostate Cancer through Exosome-Mediated Re pression of miR-200c-3p. Cancers (Basel). 13:50202021. View Article : Google Scholar : PubMed/NCBI | |
|
Sotomayor P, Godoy A, Smith GJ and Huss WJ: Oct4A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate. 69:401–410. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Quintanal-Villalonga A, Kawasaki K, Redin E, Uddin F, Rakhade S, Durani V, Sabet A, Shafer M, Karthaus WR, Zaidi S, et al: CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation. Signal Transduct Target Ther. 9:1892024. View Article : Google Scholar : PubMed/NCBI | |
|
Dardenne E, Beltran H, Benelli M, Gayvert K, Berger A, Puca L, Cyrta J, Sboner A, Noorzad Z, MacDonald T, et al: N-Myc Induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell. 30:563–577. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Berger A, Brady NJ, Bareja R, Robinson B, Conteduca V, Augello MA, Puca L, Ahmed A, Dardenne E, Lu X, et al: N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer. J Clin Invest. 129:3924–3940. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, et al: Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 1:487–495. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, Kenney AM, Schulte JH, Beijersbergen R, Christiansen H, et al: Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell. 15:67–78. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Brockmann M, Poon E, Berry T, Carstensen A, Deubzer HE, Rycak L, Jamin Y, Thway K, Robinson SP, Roels F, et al: Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell. 24:75–89. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Quintanal-Villalonga Á, Chan JM, Yu HA, Pe'er D, Sawyers CL, Sen T and Rudin CM: Lineage plasticity in cancer: A shared pathway of therapeutic resistance. Nat Rev Clin Oncol. 17:360–371. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
McQuillen CN and Brady NJ: ASCL1 drives the development of neuroendocrine prostate cancer. Cancer Res. 84:3499–3501. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Davies A, Zoubeidi A and Selth LA: The epigenetic and transcriptional landscape of neuroendocrine prostate cancer. Endocr Relat Cancer. 27:R35–R50. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Clermont PL, Lin D, Crea F, Wu R, Xue H, Wang Y, Thu KL, Lam WL, Collins CC, Wang Y, et al: Polycomb-mediated silencing in neuroendocrine prostate cancer. Clin Epigenetics. 7:402015. View Article : Google Scholar : PubMed/NCBI | |
|
Donaldson-Collier MC, Sungalee S, Zufferey M, Tavernari D, Katanayeva N, Battistello E, Mina M, Douglass KM, Rey T, Raynaud F, et al: EZH2 oncogenic mutations drive epigenetic, transcriptional, and struct ural changes within chromatin domains. Nat Genet. 51:517–528. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Sreekumar A and Saini S: Role of transcription factors and chromatin modifiers in driving linea ge reprogramming in treatment-induced neuroendocrine prostate cancer. Front Cell Dev Biol. 11:10757072023. View Article : Google Scholar : PubMed/NCBI | |
|
Paranjape AN, Soundararajan R, Werden SJ, Joseph R, Taube JH, Liu H, Rodriguez-Canales J, Sphyris N, Wistuba I, Miura N, et al: Inhibition of FOXC2 restores epithelial phenotype and drug sensitivity in prostate cancer cells with stem-cell properties. Oncogene. 35:5963–5976. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Q, Yang M, Fu J, Sun X, Wang J, Zhang H, Hu J and Han B: KIF1A promotes neuroendocrine differentiation in prostate cancer by regulating the OGT-mediated O-GlcNAcylation. Cell Death Dis. 15:7962024. View Article : Google Scholar : PubMed/NCBI | |
|
Ward C, Volpe G, Cauchy P, Ptasinska A, Almaghrabi R, Blakemore D, Nafria M, Kestner D, Frampton J, Murphy G, et al: Fine-tuning mybl2 is required for proper mesenchymal-to-epithelial transition during somatic reprogramming. Cell Rep. 24:1496–1511.e8. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
German B, Alaiwi SA, Ho KL, Nanda JS, Fonseca MA, Burkhart DL, Sheahan AV, Bergom HE, Morel KL, Beltran H, et al: MYBL2 drives prostate cancer plasticity: Inhibiting its transcriptional target CDK2 for RB1-deficient neuroendocrine prostate cancer. Cancer Res Commun. 4:2295–2307. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Hsieh CL, Do AD, Hsueh CY, Raboshakga MO, Thanh TN, Tai TT, Kung HJ and Sung SY: L1CAM mediates neuroendocrine phenotype acquisition in prostate cancer cells. Prostate. 84:1434–1447. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Ku SY, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich ZW, Goodrich MM, Labbé DP, Gomez EC, Wang J, et al: Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science. 355:78–83. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen CC, Wongvipat J, Ku SY, Gao D, Cao Z, et al: SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science. 355:84–88. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Beltran H, Oromendia C, Danila DC, Montgomery B, Hoimes C, Szmulewitz RZ, Vaishampayan U, Armstrong AJ, Stein M, Pinski J, et al: A Phase II Trial of the aurora kinase a inhibitor alisertib for patients with castration-resistant and neuroendocrine prostate cancer: Efficacy and biomarkers. Clin Cancer Res. 25:43–51. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, Majem M, Nackaerts K, Syrigos K, Hansen K, et al: Efficacy and safety of rovalpituzumab tesirine compared with topotecan as second-line therapy in DLL3-High SCLC: Results from the phase 3 TAHOE study. J Thorac Oncol. 16:1547–1558. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, Marotz C, Giannopoulou E, Chakravarthi BV, Varambally S, et al: Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 22:298–305. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Takahashi K and Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E and Xu Y: p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol. 7:165–171. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Luongo F, Colonna F, Calapà F, Vitale S, Fiori ME and De Maria R: PTEN Tumor-suppressor: The dam of stemness in cancer. Cancers (Basel). 11:10762019. View Article : Google Scholar : PubMed/NCBI | |
|
Zou M, Toivanen R, Mitrofanova A, Floch N, Hayati S, Sun Y, Le Magnen C, Chester D, Mostaghel EA, Califano A, et al: Transdifferentiation as a mechanism of treatment resistance in a mouse model of Castration-resistant prostate cancer. Cancer Discov. 7:736–749. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Tan HL, Sood A, Rahimi HA, Wang W, Gupta N, Hicks J, Mosier S, Gocke CD, Epstein JI, Netto GJ, et al: Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. Clin Cancer Res. 20:890–903. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Bracken AP, Pasini D, Capra M, Prosperini E, Colli E and Helin K: EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J. 22:5323–5335. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Song Z, Cao Q, Guo B, Zhao Y, Li X, Lou N, Zhu C, Luo G, Peng S, Li G, et al: Overexpression of RACGAP1 by E2F1 promotes neuroendocrine differentiat ion of prostate cancer by stabilizing EZH2 expression. Aging Dis. 14:1757–1774. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Z, Flesken-Nikitin A, Corney DC, Wang W, Goodrich DW, Roy-Burman P and Nikitin AY: Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 66:7889–7898. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Rajabi H and Kufe D: MUC1-C Oncoprotein integrates a program of EMT, epigenetic reprogramming and immune evasion in human carcinomas. Biochim Biophys Acta Rev Cancer. 1868:117–122. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Tong D: Unravelling the molecular mechanisms of prostate cancer evolution from genotype to phenotype. Crit Rev Oncol Hematol. 163:1033702021. View Article : Google Scholar : PubMed/NCBI | |
|
Rajabi H, Hiraki M and Kufe D: MUC1-C activates polycomb repressive complexes and downregulates tumor suppressor genes in human cancer cells. Oncogene. 37:2079–2088. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Rajabi H, Ahmad R, Jin C, Joshi MD, Guha M, Alam M, Kharbanda S and Kufe D: MUC1-C oncoprotein confers androgen-independent growth of human prostate cancer cells. Prostate. 72:1659–1668. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Hagiwara M, Yasumizu Y, Yamashita N, Rajabi H, Fushimi A, Long MD, Li W, Bhattacharya A, Ahmad R, Oya M, et al: MUC1-C activates the BAF (mSWI/SNF) complex in prostate cancer stem cells. Cancer Res. 81:1111–1122. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Chang YT, Lin TP, Campbell M, Pan CC, Lee SH, Lee HC, Yang MH, Kung HJ and Chang PC: REST is a crucial regulator for acquiring EMT-like and stemness phenotypes in hormone-refractory prostate cancer. Sci Rep. 7:427952017. View Article : Google Scholar : PubMed/NCBI | |
|
Chang YT, Lin TP, Tang JT, Campbell M, Luo YL, Lu SY, Yang CP, Cheng TY, Chang CH, Liu TT, et al: HOTAIR is a REST-regulated lncRNA that promotes neuroendocrine differe ntiation in castration resistant prostate cancer. Cancer Lett. 433:43–52. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Lin YC, Chang YT, Campbell M, Lin TP, Pan CC, Lee HC, Shih JC and Chang PC: MAOA-a novel decision maker of apoptosis and autophagy in hormone refr actory neuroendocrine prostate cancer cells. Sci Rep. 7:463382017. View Article : Google Scholar : PubMed/NCBI | |
|
Lee CF, Chen YA, Hernandez E, Pong RC, Ma S, Hofstad M, Kapur P, Zhau H, Chung LW, Lai CH, et al: The central role of Sphingosine kinase 1 in the development of neuroen docrine prostate cancer (NEPC): A new targeted therapy of NEPC. Clin Transl Med. 12:e6952022. View Article : Google Scholar : PubMed/NCBI | |
|
O'Reilly D, Johnson P and Buchanan PJ: Hypoxia induced cancer stem cell enrichment promotes resistance to androgen deprivation therapy in prostate cancer. Steroids. 152:1084972019. View Article : Google Scholar : PubMed/NCBI | |
|
Alumkal JJ, Sun D, Lu E, Beer TM, Thomas GV, Latour E, Aggarwal R, Cetnar J, Ryan CJ, Tabatabaei S, et al: Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance. Proc Natl Acad SciUSA. 117:12315–12323. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Bishop JL, Thaper D and Zoubeidi A: The multifaceted roles of STAT3 signaling in the progression of prostate cancer. Cancers. 6:829–859. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Albino D, Civenni G, Rossi S, Mitra A, Catapano CV and Carbone GM: The ETS factor ESE3/EHF represses IL-6 preventing STAT3 activation and expansion of the prostate cancer stem-like compartment. Oncotarget. 7:76756–76768. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Song N, Cui K, Zeng L, Li M, Fan Y, Shi P, Wang Z, Su W and Wang H: Advance in the role of chemokines/chemokine receptors in carcinogenesis: Focus on pancreatic cancer. Eur J Pharmacol. 967:1763572024. View Article : Google Scholar : PubMed/NCBI | |
|
Liu RY, Zeng Y, Lei Z, Wang L, Yang H, Liu Z, Zhao J and Zhang HT: JAK/STAT3 signaling is required for TGF-β-induced epithelial-mesenchymal transition in lung cancer cells. Int J Oncol. 44:1643–1651. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Deng S, Wang C, Wang Y, Xu Y, Li X, Johnson NA, Mukherji A, Lo UG, Xu L, Gonzalez J, et al: Ectopic JAK-STAT activation enables the transition to a stem-like and multilineage state conferring AR-targeted therapy resistance. Nat Cancer. 3:1071–1087. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Ware KE, Thomas BC, Olawuni PD, Sheth MU, Hawkey N, Yeshwanth M, Miller BC, Vietor KJ, Jolly MK, Kim SY, et al: A synthetic lethal screen for Snail-induced enzalutamide resistance identifies JAK/STAT signaling as a therapeutic vulnerability in prostate cancer. Front Mol Biosci. 10:11045052023. View Article : Google Scholar : PubMed/NCBI | |
|
Chen L, Wang Y and Zhang B: Hypermethylation in the promoter region inhibits AJAP1 expression and activates the JAK/STAT pathway to promote prostate cancer cell migration and stem cell sphere formation. Pathol Res Pract. 241:1542242023. View Article : Google Scholar : PubMed/NCBI | |
|
Spiotto MT and Chung TD: STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells. Prostate. 42:186–195. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Smith ND, Schulze-Hoepfner FT, Veliceasa D, Filleur S, Shareef S, Huang L, Huang XM and Volpert OV: Pigment Epithelium-derived factor and interleukin-6 control prostate neuroendocrine differentiation via feed-forward mechanism. J Urol. 179:2427–2434. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Dai J, Keller J, Zhang J, Lu Y, Yao Z and Keller ET: Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res. 65:8274–8285. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, García-Echeverría C, Schultz PG and Reddy VA: The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci USA. 106:268–273. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang A, Lau NA, Wong A, Brown LG, Coleman IM, De Sarkar N, Li D, DeLucia DC, Labrecque MP, Nguyen HM, et al: Concurrent targeting of HDAC and PI3K to overcome phenotypic heterogeneity of castration-resistant and neuroendocrine prostate cancers. Cancer Res Commun. 3:2358–2374. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Wu J, Cang S, Liu C, Ochiai W and Chiao JW: Development of human prostate cancer stem cells involves epigenomic alteration and PI3K/AKT pathway activation. Exp Hematol Oncol. 9:122020. View Article : Google Scholar : PubMed/NCBI | |
|
Morell C, Bort A, Vara D, Ramos-Torres A, Rodríguez-Henche N and Díaz-Laviada I: The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis. 19:248–257. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Gonzalez DM and Medici D: Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal. 7:re82014. View Article : Google Scholar : PubMed/NCBI | |
|
Yoo YA, Kang MH, Kim JS and Oh SC: Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGF-beta-mediated activation of the ALK5-Smad 3 pathway. Carcinogenesis. 29:480–490. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Petrova R and Joyner AL: Roles for Hedgehog signaling in adult organ homeostasis and repair. Development. 141:3445–3457. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Merchant AA and Matsui W: Targeting Hedgehog-a cancer stem cell pathway. Clin Cancer Res. 16:3130–3140. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Chang HH, Chen BY, Wu CY, Tsao ZJ, Chen YY, Chang CP, Yang CR and Lin DP: Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model. J Biomed Sci. 18:62011. View Article : Google Scholar : PubMed/NCBI | |
|
Wang L, Li H, Li Z, Li M, Tang Q, Wu C and Lu Z: Smoothened loss is a characteristic of neuroendocrine prostate cancer. Prostate. 81:508–520. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Kishore C and Zi X: Wnt Signaling and therapeutic resistance in castration-resistant prostate cancer. Curr Pharmacol Rep. 9:261–274. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Sha J, Han Q, Chi C, Zhu Y, Pan J, Dong B, Huang Y, Xia W and Xue W: PRKAR2B promotes prostate cancer metastasis by activating Wnt/β-catenin and inducing epithelial-mesenchymal transition. J Cell Biochem. 119:7319–7327. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Duchartre Y, Kim YM and Kahn M: The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol. 99:141–149. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Bisson I and Prowse DM: WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics. Cell Res. 19:683–697. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Pan KF, Lee WJ, Chou CC, Yang YC, Chang YC, Chien MH, Hsiao M and Hua KT: Direct interaction of β-catenin with nuclear ESM1 supports stemness of metastatic prostate cancer. EMBO J. 40:e1054502021. View Article : Google Scholar : PubMed/NCBI | |
|
Manzar N, Khan UK, Goel A, Carskadon S, Gupta N, Palanisamy N and Ateeq B: An integrative proteomics approach identifies tyrosine kinase KIT as a therapeutic target for SPINK1-positive prostate cancer. iScience. 27:1087942024. View Article : Google Scholar : PubMed/NCBI | |
|
Bland T, Wang J, Yin L, Pu T, Li J, Gao J, Lin TP, Gao AC and Wu BJ: WLS-Wnt signaling promotes neuroendocrine prostate cancer. iScience. 24:1019702021. View Article : Google Scholar : PubMed/NCBI | |
|
Uysal-Onganer P, Kawano Y, Caro M, Walker MM, Diez S, Darrington RS, Waxman J and Kypta RM: Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells. Mol Cancer. 9:552010. View Article : Google Scholar : PubMed/NCBI | |
|
Liu RJ, Xu ZP, Huang X, Xu B and Chen M: Yin Yang 1 promotes the neuroendocrine differentiation of prostate cancer cells via the non-canonical WNT pathway (FYN/STAT3). Clin Transl Med. 13:e14222023. View Article : Google Scholar : PubMed/NCBI | |
|
Wen YC, Liu YN, Yeh HL, Chen WH, Jiang KC, Lin SR, Huang J, Hsiao M and Chen WY: TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer. Oncogenesis. 10:812021. View Article : Google Scholar : PubMed/NCBI | |
|
Terry S, Maillé P, Baaddi H, Kheuang L, Soyeux P, Nicolaiew N, Ceraline J, Firlej V, Beltran H, Allory Y, et al: Cross modulation between the androgen receptor axis and protocadherin-PC in mediating neuroendocrine transdifferentiation and therapeutic resistance of prostate cancer. Neoplasia. 15:761–772. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Shan J, Al-Muftah MA, Al-Kowari MK, Abuaqel SWJ, Al-Rumaihi K, Al-Bozom I, Li P and Chouchane L: Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer. Cell Death Discov. 5:1392019. View Article : Google Scholar : PubMed/NCBI | |
|
Unno K, Chalmers ZR, Pamarthy S, Vatapalli R, Rodriguez Y, Lysy B, Mok H, Sagar V, Han H, Yoo YA, et al: Activated ALK cooperates with N-Myc via Wnt/β-Catenin signaling to induce neuroendocrine prostate cancer. Cancer Res. 81:2157–2170. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Kar R, Jha NK, Jha SK, Sharma A, Dholpuria S, Asthana N, Chaurasiya K, Singh VK, Burgee S and Nand P: A ‘NOTCH’ Deeper into the Epithelial-To-Mesenchymal Transition (EMT) program in breast cancer. Genes (Basel). 10:9612019. View Article : Google Scholar : PubMed/NCBI | |
|
Timmerman LA, Grego-Bessa J, Raya A, Bertrán E, Pérez-Pomares JM, Díez J, Aranda S, Palomo S, McCormick F, Izpisúa-Belmonte JC, et al: Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 18:99–115. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Uribe-Etxebarria V, Pineda JR, García-Gallastegi P, Agliano A, Unda F and Ibarretxe G: Notch and wnt signaling modulation to enhance DPSC stemness and therapeutic potential. Int J Mol Sci. 24:73892023. View Article : Google Scholar : PubMed/NCBI | |
|
Puca L, Gavyert K, Sailer V, Conteduca V, Dardenne E, Sigouros M, Isse K, Kearney M, Vosoughi A, Fernandez L, et al: Delta-like protein 3 expression and therapeutic targeting in neuroendo crine prostate cancer. Sci Transl Med. 11:eaav08912019. View Article : Google Scholar : PubMed/NCBI | |
|
Danza G, Di Serio C, Rosati F, Lonetto G, Sturli N, Kacer D, Pennella A, Ventimiglia G, Barucci R, Piscazzi A, et al: Notch signaling modulates hypoxia-induced neuroendocrine differentiati on of human prostate cancer cells. Mol Cancer Res. 10:230–238. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Menssouri N, Poiraudeau L, Helissey C, Bigot L, Sabio J, Ibrahim T, Pobel C, Nicotra C, Ngo-Camus M, Lacroix L, et al: Genomic profiling of metastatic castration-resistant prostate cancer s amples resistant to androgen-receptor pathway inhibitors. Clin Cancer Res. 29:4504–4517. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Docherty NG, O'Sullivan OE, Healy DA, Murphy M, O'Neill AJ, Fitzpatrick JM and Watson RW: TGF-beta1-induced EMT can occur independently of its proapoptotic effects and is aided by EGF receptor activation. Am J Physiol Renal Physiol. 290:F1202–F1212. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Yu B, Su J, Shi Q, Liu Q, Ma J, Ru G, Zhang L, Zhang J, Hu X and Tang J: KMT5A-methylated SNIP1 promotes triple-negative breast cancer metastasis by activating YAP signaling. Nat Commun. 13:21922022. View Article : Google Scholar : PubMed/NCBI | |
|
Jiao C, Meng T, Zhou C, Wang X, Wang P, Lu M, Tan X, Wei Q, Ge X and Jin J: TGF-β signaling regulates SPOP expression and promotes prostate cancer cell stemness. Aging (Albany NY). 12:7747–7760. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Natani S, Sruthi KK, Asha SM, Khilar P, Lakshmi PSV and Ummanni R: Activation of TGF-β-SMAD2 signaling by IL-6 drives neuroendocrine differentiation of prostate cancer through p38MAPK. Cell Signal. 91:1102402022. View Article : Google Scholar : PubMed/NCBI | |
|
Wen S, Hou Y, Fu L, Xi L, Yang D, Zhao M, Qin Y, Sun K, Teng Y and Liu M: Cancer-associated fibroblast (CAF)-derived IL32 promotes breast cancer cell invasion and metastasis via integrin β3-p38 MAPK signalling. Cancer Lett. 442:320–332. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Tang T, Wang LX, Yang ML and Zhang RM: lncRNA TPTEP1 inhibits stemness and radioresistance of glioma through miR-106a-5p-mediated P38 MAPK signaling. Mol Med Rep. 22:4857–4867. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Du Y, Long Q, Zhang L, Shi Y, Liu X, Li X, Guan B, Tian Y, Wang X, Li L and He D: Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling. Int J Oncol. 47:2064–2072. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Han H, Li H, Ma Y, Zhao Z, An Q, Zhao J and Shi C: Monoamine oxidase A (MAOA): A promising target for prostate cancer therapy. Cancer Lett. 563:2161882023. View Article : Google Scholar : PubMed/NCBI | |
|
Weng CC, Ding PY, Liu YH, Hawse JR, Subramaniam M, Wu CC, Lin YC, Chen CY, Hung WC and Cheng KH: Mutant Kras-induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis. Oncogene. 38:2005–2019. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
De Luca P, Moiola CP, Zalazar F, Gardner K, Vazquez ES and De Siervi A: BRCA1 and p53 regulate critical prostate cancer pathways. Prostate Cancer Prostatic Dis. 16:233–238. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Zhang YX, Kong CZ, Zhang Z and Zhu YY: Loss of P53 facilitates invasion and metastasis of prostate cancer cells. Mol Cell Biochem. 384:121–127. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Ren D, Wang M, Guo W, Zhao X, Tu X, Huang S, Zou X and Peng X: Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR-145. Int J Oncol. 42:1473–1481. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kogan-Sakin I, Tabach Y, Buganim Y, Molchadsky A, Solomon H, Madar S, Kamer I, Stambolsky P, Shelly A, Goldfinger N, et al: Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial-mesenchymal transition in immortalized prostate cells. Cell Death Differ. 18:271–281. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Kumaraswamy A, Duan Z, Flores D, Zhang C, Sehrawat A, Hu YM, Swaim OA, Rodansky E, Storck WK, Kuleape JA, et al: LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function. JCI Insight. 8:e1674402023. View Article : Google Scholar : PubMed/NCBI | |
|
Chaves LP, Melo CM, Saggioro FP, Reis RBD and Squire JA: Epithelial-mesenchymal transition signaling and prostate cancer stem cells: Emerging biomarkers and opportunities for precision therapeutics. Genes (Basel). 12:19002021. View Article : Google Scholar : PubMed/NCBI | |
|
Sadrkhanloo M, Paskeh MDA, Hashemi M, Raesi R, Bahonar A, Nakhaee Z, Entezari M, Beig Goharrizi MAS, Salimimoghadam S, Ren J, et al: New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis. Pathol Res Pract. 251:1549022023. View Article : Google Scholar : PubMed/NCBI | |
|
Mei W, Lin X, Kapoor A, Gu Y, Zhao K and Tang D: The contributions of prostate cancer stem cells in prostate cancer initiation and metastasis. Cancers (Basel). 11:4342019. View Article : Google Scholar : PubMed/NCBI | |
|
Kaushik G, Seshacharyulu P, Rauth S, Nallasamy P, Rachagani S, Nimmakayala RK, Vengoji R, Mallya K, Chirravuri-Venkata R, Singh AB, et al: Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis. Oncogene. 40:848–862. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Q, Pang J, Wang LA, Huang Z, Xu J, Yang X, Xie Q, Huang Y, Tang T, Tong D, et al: Histone demethylase PHF8 drives neuroendocrine prostate cancer progres sion by epigenetically upregulating FOXA2. J Pathol. 253:106–118. 253 View Article : Google Scholar : PubMed/NCBI | |
|
Qi J, Pellecchia M and Ronai ZeA: The Siah2-HIF-FoxA2 axis in prostate cancer-new markers and therapeu tic opportunities. Oncotarget. 1:379–385. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Qi J, Nakayama K, Cardiff RD, Borowsky AD, Kaul K, Williams R, Krajewski S, Mercola D, Carpenter PM, Bowtell D, et al: Siah2-dependent concerted activity of HIF and FoxA2 regulates formatio n of neuroendocrine phenotype and neuroendocrine prostate tumors. Cancer Cell. 18:23–38. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Masone MC: FOXA2-KIT-driven lineage plasticity in NEPC. Nat Rev Urol. 20:82023. View Article : Google Scholar | |
|
Singh N, Padi SKR, Bearss JJ, Pandey R, Okumura K, Beltran H, Song JH, Kraft AS and Olive V: PIM protein kinases regulate the level of the long noncoding RNA H19 t o control stem cell gene transcription and modulate tumor growth. Mol Oncol. 14:974–990. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lee AR, Gan Y, Tang Y and Dong X: A novel mechanism of SRRM4 in promoting neuroendocrine prostate cancer development via a pluripotency gene network. EBioMedicine. 35:167–177. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Fan L, Gong Y, He Y, Gao WQ, Dong X, Dong B, Zhu HH and Xue W: TRIM59 is suppressed by androgen receptor and acts to promote lineage plasticity and treatment-induced neuroendocrine differentiation in pro state cancer. Oncogene. 42:559–571. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Monga J, Adrianto I, Rogers C, Gadgeel S, Chitale D, Alumkal JJ, Beltran H, Zoubeidi A and Ghosh J: Tribbles 2 pseudokinase confers enzalutamide resistance in prostate ca ncer by promoting lineage plasticity. J Biol Chem. 298:1015562022. View Article : Google Scholar : PubMed/NCBI | |
|
Kim S, Thaper D, Bidnur S, Toren P, Akamatsu S, Bishop JL, Colins C, Vahid S and Zoubeidi A: PEG10 is associated with treatment-induced neuroendocrine prostate can cer. J Mol Endocrinol. 63:39–49. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Yoshie H, Sedukhina AS, Minagawa K, Oda K, Ohnuma S, Yanagisawa N, Maeda I, Takagi M, Kudo H, Nakazawa R, et al: A bioinformatics-to-clinic sequential approach to analysis of prostate cancer biomarkers using TCGA datasets and clinical samples: A new met hod for precision oncology? Oncotarget. 8:99601–99611. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Choi WW, Boland JL and Lin J: ONECUT2 as a key mediator of androgen receptor-independent cell growth and neuroendocrine differentiation in castration-resistant prostate c ancer. Cancer Drug Resist. 5:165–170. 2022.PubMed/NCBI | |
|
Tenjin Y, Kudoh S, Kubota S, Yamada T, Matsuo A, Sato Y, Ichimura T, Kohrogi H, Sashida G, Sakagami T and Ito T: Ascl1-induced Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in small-cell lung cancer and Wnt11 regulates small-cell lung cancer biology. Lab Invest. 99:1622–1635. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
DeLucia DC, Cardillo TM, Ang L, Labrecque MP, Zhang A, Hopkins JE, De Sarkar N, Coleman I, da Costa RMG, Corey E, et al: Regulation of CEACAM5 and Therapeutic Efficacy of an Anti-CEACAM5-SN38 Antibody-drug conjugate in neuroendocrine prostate cancer. Clin Cancer Res. 27:759–774. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Meder L, König K, Ozretić L, Schultheis AM, Ueckeroth F, Ade CP, Albus K, Boehm D, Rommerscheidt-Fuss U, Florin A, et al: NOTCH, ASCL1, p53 and RB alterations define an alternative pathway dri ving neuroendocrine and small cell lung carcinomas. Int J Cancer. 138:927–938. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Tang Q, Chen J, Di Z, Yuan W, Zhou Z, Liu Z, Han S, Liu Y, Ying G, Shu X, et al: TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer. J Exp Clin Cancer Res. 39:2322020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Wang X, Kim M, He D, Wang C, Fong KW and Liu X: Downregulation of EZH2 inhibits epithelial-mesenchymal transition in enzalutamide-resistant prostate cancer. Prostate. 83:1458–1469. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Mirzaei S, Gholami MH, Hushmandi K, Hashemi F, Zabolian A, Canadas I, Zarrabi A, Nabavi N, Aref AR, Crea F, et al: The long and short non-coding RNAs modulating EZH2 signaling in cancer. J Hematol Oncol. 15:182022. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang W, Bado IL, Hu J, Wan YW, Wu L, Wang H, Gao Y, Jeong HH, Xu Z, Hao X, et al: The bone microenvironment invigorates metastatic seeds for further dissemination. Cell. 184:2471–2486.e20. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Kufe D: Dependence on MUC1-C in progression of neuroendocrine prostate cancer. Int J Mol Sci. 24:37192023. View Article : Google Scholar : PubMed/NCBI |
