
O‑GlcNAcylation as an emerging molecular target for cholangiocarcinoma therapy (Review)
- Authors:
- Purin Charoensuksai
- Siwanon Jirawatnotai
-
Affiliations: Department of Biomedicine and Health Informatics, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand, Siriraj Center of Research Excellence for Precision Medicine and Systems Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand - Published online on: July 18, 2025 https://doi.org/10.3892/or.2025.8952
- Article Number: 119
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Copyright: © Charoensuksai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
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Torres CR and Hart GW: Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. J Biol Chem. 259:3308–3317. 1984. View Article : Google Scholar : PubMed/NCBI | |
Haltiwanger RS, Blomberg MA and Hart GW: Glycosylation of nuclear and cytoplasmic proteins. Purification and characterization of a uridine diphospho-N-acetylglucosamine: Polypeptide beta-N-acetylglucosaminyltransferase. J Biol Chem. 267:9005–9013. 1992. View Article : Google Scholar : PubMed/NCBI | |
Kreppel LK, Blomberg MA and Hart GW: Dynamic glycosylation of nuclear and cytosolic proteins. Cloning and characterization of a unique O-GlcNAc transferase with multiple tetratricopeptide repeats. J Biol Chem. 272:9308–9315. 1997. View Article : Google Scholar : PubMed/NCBI | |
Starr CM and Hanover JA: Glycosylation of nuclear pore protein p62. Reticulocyte lysate catalyzes O-linked N-acetylglucosamine addition in vitro. J Biol Chem. 265:6868–6873. 1990. View Article : Google Scholar : PubMed/NCBI | |
Gao Y, Wells L, Comer FI, Parker GJ and Hart GW: Dynamic O-glycosylation of nuclear and cytosolic proteins: Cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J Biol Chem. 276:9838–9845. 2001. View Article : Google Scholar : PubMed/NCBI | |
Dong DL and Hart GW: Purification and characterization of an O-GlcNAc selective N-acetyl-beta-D-glucosaminidase from rat spleen cytosol. J Biol Chem. 269:19321–19330. 1994. View Article : Google Scholar : PubMed/NCBI | |
Nolte D and Müller U: Human O-GlcNAc transferase (OGT): Genomic structure, analysis of splice variants, fine mapping in Xq13.1. Mamm Genome. 13:62–64. 2002. View Article : Google Scholar : PubMed/NCBI | |
Hanover JA, Yu S, Lubas WB, Shin SH, Ragano-Caracciola M, Kochran J and Love DC: Mitochondrial and nucleocytoplasmic isoforms of O-linked GlcNAc transferase encoded by a single mammalian gene. Arch Biochem Biophys. 409:287–297. 2003. View Article : Google Scholar : PubMed/NCBI | |
Lu Q, Zhang X, Liang T and Bai X: O-GlcNAcylation: An important post-translational modification and a potential therapeutic target for cancer therapy. Mol Med. 28:1152022. View Article : Google Scholar : PubMed/NCBI | |
Love DC, Kochan J, Cathey RL, Shin SH and Hanover JA: Mitochondrial and nucleocytoplasmic targeting of O-linked GlcNAc transferase. J Cell Sci. 116:647–654. 2003. View Article : Google Scholar : PubMed/NCBI | |
Lubas WA, Frank DW, Krause M and Hanover JA: O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats. J Biol Chem. 272:9316–9324. 1997. View Article : Google Scholar : PubMed/NCBI | |
Stephen HM, Adams TM and Wells L: Regulating the regulators: mechanisms of substrate selection of the O-GlcNAc cycling enzymes OGT and OGA. Glycobiology. 31:724–733. 2021. View Article : Google Scholar : PubMed/NCBI | |
Boyd SS, Robarts DR, Nguyen K, Villar M, Alghusen IM, Kotulkar M, Denson A, Fedosyuk H, Whelan SA, Lee NCY, et al: Multi-omics after O-GlcNAc alteration identified cellular processes promoting aneuploidy after loss of O-GlcNAc transferase. Mol Metab. 90:1020602024. View Article : Google Scholar : PubMed/NCBI | |
Levine ZG, Potter SC, Joiner CM, Fei GQ, Nabet B, Sonnett M, Zachara NE, Gray NS, Paulo JA and Walker S: Mammalian cell proliferation requires noncatalytic functions of O-GlcNAc transferase. Proc Natl Acad Sci USA. 118:e20167781182021. View Article : Google Scholar : PubMed/NCBI | |
Tang J, Long G, Li X, Zhou L, Zhou Y and Wu Z: The deubiquitinase EIF3H promotes hepatocellular carcinoma progression by stabilizing OGT and inhibiting ferroptosis. Cell Commun Signal. 21:1982023. View Article : Google Scholar : PubMed/NCBI | |
Marshall S, Bacote V and Traxinger RR: Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem. 266:4706–4712. 1991. View Article : Google Scholar : PubMed/NCBI | |
Hanover JA, Krause MW and Love DC: The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine. Biochim Biophys Acta. 1800:80–95. 2010. View Article : Google Scholar : PubMed/NCBI | |
Lam C, Low JY, Tran PT and Wang H: The hexosamine biosynthetic pathway and cancer: Current knowledge and future therapeutic strategies. Cancer Lett. 503:11–18. 2021. View Article : Google Scholar : PubMed/NCBI | |
Morales MM and Pratt MR: The post-translational modification O-GlcNAc is a sensor and regulator of metabolism. Open Biol. 14:2402092024. View Article : Google Scholar : PubMed/NCBI | |
Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, Cardinale V, Carpino G, Andersen JB, Braconi C, et al: Cholangiocarcinoma 2020: The next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 17:557–588. 2020. View Article : Google Scholar : PubMed/NCBI | |
Bertuccio P, Malvezzi M, Carioli G, Hashim D, Boffetta P, El-Serag HB, La Vecchia C and Negri E: Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 71:104–114. 2019. View Article : Google Scholar : PubMed/NCBI | |
Qurashi M, Vithayathil M and Khan SA: Epidemiology of cholangiocarcinoma. Eur J Surg Oncol. 51:1070642025. View Article : Google Scholar : PubMed/NCBI | |
Razumilava N and Gores GJ: Cholangiocarcinoma. Lancet. 383:2168–2179. 2014. View Article : Google Scholar : PubMed/NCBI | |
Benson AB, D'Angelica MI, Abrams T, Abbott DE, Ahmed A, Anaya DA, Anders R, Are C, Bachini M, Binder D, et al: NCCN guidelines® insights: Biliary tract cancers, version 2.2023. J Natl Compr Cancer Netw. 21:694–704. 2023. View Article : Google Scholar : PubMed/NCBI | |
Vogel A, Bridgewater J, Edeline J, Kelley RK, Klümpen HJ, Malka D, Primrose JN, Rimassa L, Stenzinger A, Valle JW, et al: Biliary tract cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 34:127–140. 2023. View Article : Google Scholar : PubMed/NCBI | |
Valle JW, Lamarca A, Goyal L, Barriuso J and Zhu AX: New horizons for precision medicine in biliary tract cancers. Cancer Discov. 7:943–962. 2017. View Article : Google Scholar : PubMed/NCBI | |
Tsilimigras DI, Endo Y, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Popescu I, Poultsides GA, Maithel SK, Marques HP, et al: Recurrent intrahepatic cholangiocarcinoma: A 10-point score to predict post-recurrence survival and guide treatment of recurrence. Ann Surg Oncol. 31:4427–4435. 2024. View Article : Google Scholar : PubMed/NCBI | |
Groot Koerkamp B, Wiggers JK, Allen PJ, Besselink MG, Blumgart LH, Busch OR, Coelen RJ, D'Angelica MI, DeMatteo RP, Gouma DJ, et al: Recurrence rate and pattern of perihilar cholangiocarcinoma after curative intent resection. J Am Coll Surg. 221:1041–1049. 2015. View Article : Google Scholar : PubMed/NCBI | |
Komaya K, Ebata T, Shirai K, Ohira S, Morofuji N, Akutagawa A, Yamaguchi R and Nagino M; Nagoya Surgical Oncology Group, : Recurrence after resection with curative intent for distal cholangiocarcinoma. Br J Surg. 104:426–433. 2017. View Article : Google Scholar : PubMed/NCBI | |
Qiao Z, Dang C, Zhou B, Zhang W, Jiang J, Zhang J, Kong R and Ma Y: O-linked N-acetylglucosamine transferase (OGT) is overexpressed and promotes O-linked protein glycosylation in esophageal squamous cell carcinoma. J Biomed Res. 26:268–273. 2012. View Article : Google Scholar : PubMed/NCBI | |
Jiang M, Qiu Z, Zhang S, Fan X, Cai X, Xu B, Li X, Zhou J, Zhang X, Chu Y, et al: Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling. Oncotarget. 7:61390–61402. 2016. View Article : Google Scholar : PubMed/NCBI | |
Jang TJ and Kim UJ: O-GlcNAcylation is associated with the development and progression of gastric carcinoma. Pathol Res Pract. 212:622–630. 2016. View Article : Google Scholar : PubMed/NCBI | |
Sharma NS, Gupta VK, Dauer P, Kesh K, Hadad R, Giri B, Chandra A, Dudeja V, Slawson C, Banerjee S, et al: O-GlcNAc modification of Sox2 regulates self-renewal in pancreatic cancer by promoting its stability. Theranostics. 9:3410–3424. 2019. View Article : Google Scholar : PubMed/NCBI | |
Santos-Laso A, Perugorria MJ and Banales JM: O-GlcNAcylation: Undesired tripmate but an opportunity for treatment in NAFLD-HCC. J Hepatol. 67:218–220. 2017. View Article : Google Scholar : PubMed/NCBI | |
Xu W, Zhang X, Wu JL, Fu L, Liu K, Liu D, Chen GG, Lai PB, Wong N and Yu J: O-GlcNAc transferase promotes fatty liver-associated liver cancer through inducing palmitic acid and activating endoplasmic reticulum stress. J Hepatol. 67:310–320. 2017. View Article : Google Scholar : PubMed/NCBI | |
Mi W, Gu Y, Han C, Liu H, Fan Q, Zhang X, Cong Q and Yu W: O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochim Biophys Acta. 1812:514–519. 2011. View Article : Google Scholar : PubMed/NCBI | |
Phueaouan T, Chaiyawat P, Netsirisawan P, Chokchai-chamnankit D, Punyarit P, Srisomsap C, Svasti J and Champattanachai V: Aberrant O-GlcNAc-modified proteins expressed in primary colorectal cancer. Oncol Rep. 30:2929–2936. 2013. View Article : Google Scholar : PubMed/NCBI | |
Phoomak C, Silsirivanit A, Wongkham C, Sripa B, Puapairoj A and Wongkham S: Overexpression of O-GlcNAc-transferase associates with aggressiveness of mass-forming cholangiocarcinoma. Asian Pac J Cancer Prev. 13 (Suppl):S101–S105. 2012.PubMed/NCBI | |
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, et al: Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 6:pl12013. View Article : Google Scholar : PubMed/NCBI | |
Su Z, Gao A, Li X, Zou S, He C, Wu J, Ding WQ and Zhou J: DNA polymerase iota promotes esophageal squamous cell carcinoma proliferation through Erk-OGT-induced G6PD overactivation. Front Oncol. 11:7063372021. View Article : Google Scholar : PubMed/NCBI | |
Xu D, Wang W, Bian T, Yang W, Shao M and Yang H: Increased expression of O-GlcNAc transferase (OGT) is a biomarker for poor prognosis and allows tumorigenesis and invasion in colon cancer. Int J Clin Exp Pathol. 12:1305–1314. 2019.PubMed/NCBI | |
Lei Y, Chen T, Li Y, Shang M, Zhang Y, Jin Y, Yu Q, Guo F and Wang T: O-GlcNAcylation of PFKFB3 is required for tumor cell proliferation under hypoxia. Oncogenesis. 9:212020. View Article : Google Scholar : PubMed/NCBI | |
Liu Q, Tao T, Liu F, Ni R, Lu C and Shen A: Hyper-O-GlcNAcylation of YB-1 affects Ser102 phosphorylation and promotes cell proliferation in hepatocellular carcinoma. Exp Cell Res. 349:230–238. 2016. View Article : Google Scholar : PubMed/NCBI | |
Gao S, Miao Y, Liu Y, Liu X, Fan X, Lin Y, Qian P, Zhou J, Dai Y, Xia L, et al: Reciprocal regulation between O-GlcNAcylation and β-catenin facilitates cell viability and inhibits apoptosis in liver cancer. DNA Cell Biol. 38:286–296. 2019. View Article : Google Scholar : PubMed/NCBI | |
Wang J, Wang Z, Yuan J, Wang J and Shen X: The positive feedback between ACSL4 expression and O-GlcNAcylation contributes to the growth and survival of hepatocellular carcinoma. Aging (Albany NY). 12:7786–7800. 2020. View Article : Google Scholar : PubMed/NCBI | |
Tang Z, Li C, Kang B, Gao G, Li C and Zhang Z: GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45((W1)): W98–W102. 2017. View Article : Google Scholar : PubMed/NCBI | |
He X, Li Y, Chen Q, Zheng L, Lou J, Lin C, Gong J, Zhu Y and Wu Y: O-GlcNAcylation and stablization of SIRT7 promote pancreatic cancer progression by blocking the SIRT7-REGγ interaction. Cell Death Differ. 29:1970–1981. 2022. View Article : Google Scholar : PubMed/NCBI | |
Guo H, Zhang B, Nairn AV, Moremen KW, Buckhaults P and Pierce M: O-linked N-acetylglucosamine (O-GlcNAc) expression levels epigenetically regulate colon cancer tumorigenesis by affecting the cancer stem cell compartment via modulating expression of transcriptional factor MYBL1. J Biol Chem. 292:4123–4137. 2017. View Article : Google Scholar : PubMed/NCBI | |
Ma Z, Vocadlo DJ and Vosseller K: Hyper-O-GlcNAcylation is anti-apoptotic and maintains constitutive NF-κB activity in pancreatic cancer cells. J Biol Chem. 288:15121–15130. 2013. View Article : Google Scholar : PubMed/NCBI | |
Steenackers A, Olivier-Van Stichelen S, Baldini SF, Dehennaut V, Toillon RA, Le Bourhis X, El Yazidi-Belkoura I and Lefebvre T: Silencing the nucleocytoplasmic O-GlcNAc transferase reduces proliferation, adhesion, and migration of cancer and fetal human colon cell lines. Front Endocrinol (Lausanne). 7:462016. View Article : Google Scholar : PubMed/NCBI | |
Wang H, Sun J, Sun H, Wang Y, Lin B, Wu L, Qin W, Zhu Q and Yi W: The OGT-c-Myc-PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth. Cell Death Differ. 31:1157–1169. 2024. View Article : Google Scholar : PubMed/NCBI | |
Drury J, Geisen ME, Tessmann JW, Rychahou PG, Kelson CO, He D, Wang C, Evers BM and Zaytseva YY: Overexpression of fatty acid synthase upregulates glutamine-fructose-6-phosphate transaminase 1 and O-linked N-acetylglucosamine transferase to increase O-GlcNAc protein glycosylation and promote colorectal cancer growth. Int J Mol Sci. 25:48832024. View Article : Google Scholar : PubMed/NCBI | |
Cao B, Duan M, Xing Y, Liu C, Yang F, Li Y, Yang T, Wei Y, Gao Q and Jiang J: O-GlcNAc transferase activates stem-like cell potential in hepatocarcinoma through O-GlcNAcylation of eukaryotic initiation factor 4E. J Cell Mol Med. 23:2384–2398. 2019. View Article : Google Scholar : PubMed/NCBI | |
Qiao Y, Zhang X, Zhang Y, Wang Y, Xu Y, Liu X, Sun F and Wang J: High glucose stimulates tumorigenesis in hepatocellular carcinoma cells through AGER-dependent O-GlcNAcylation of c-Jun. Diabetes. 65:619–632. 2016. View Article : Google Scholar : PubMed/NCBI | |
Lee SJ and Kwon OS: O-GlcNAc transferase inhibitor synergistically enhances doxorubicin-induced apoptosis in HepG2 Cells. Cancers (Basel). 12:31542020. View Article : Google Scholar : PubMed/NCBI | |
de Queiroz RM, Moon SH and Prives C: O-GlcNAc transferase regulates p21 protein levels and cell proliferation through the FoxM1-Skp2 axis in a p53-independent manner. J Biol Chem. 298:1022892022. View Article : Google Scholar : PubMed/NCBI | |
Qiu H, Liu F, Tao T, Zhang D, Liu X, Zhu G, Xu Z, Ni R and Shen A: Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. Mol Carcinog. 56:258–271. 2017. View Article : Google Scholar : PubMed/NCBI | |
Shin H, Cha HJ, Na K, Lee MJ, Cho JY, Kim CY, Kim EK, Kang CM, Kim H and Paik YK: O-GlcNAcylation of the tumor suppressor FOXO3 triggers aberrant cancer cell growth. Cancer Res. 78:1214–1224. 2018. View Article : Google Scholar : PubMed/NCBI | |
Very N, Steenackers A, Dubuquoy C, Vermuse J, Dubuquoy L, Lefebvre T and El Yazidi-Belkoura I: Cross regulation between mTOR signaling and O-GlcNAcylation. J Bioenerg Biomembr. 50:213–222. 2018. View Article : Google Scholar : PubMed/NCBI | |
Sodi VL, Khaku S, Krutilina R, Schwab LP, Vocadlo DJ, Seagroves TN and Reginato MJ: mTOR/MYC axis regulates O-GlcNAc transferase expression and O-GlcNAcylation in breast cancer. Mol Cancer Res. 13:923–933. 2015. View Article : Google Scholar : PubMed/NCBI | |
Jin L, Yuan F, Dai G, Yao Q, Xiang H, Wang L, Xue B, Shan Y and Liu X: Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells. Cell Mol Biol Lett. 25:172020. View Article : Google Scholar : PubMed/NCBI | |
Cork GK, Thompson J and Slawson C: Real talk: The inter-play between the mTOR, AMPK, and hexosamine biosynthetic pathways in cell signaling. Front Endocrinol (Lausanne). 9:5222018. View Article : Google Scholar : PubMed/NCBI | |
Ravindran Menon D, Hammerlindl H, Gimenez G, Hammerlindl S, Zuegner E, Torrano J, Bordag N, Emran AA, Giam M, Denil S, et al: H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase. Drug Resist Updat. 71:1009932023. View Article : Google Scholar : PubMed/NCBI | |
Ishimura E, Nakagawa T, Moriwaki K, Hirano S, Matsumori Y and Asahi M: Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line. Cancer Sci. 108:2373–2382. 2017. View Article : Google Scholar : PubMed/NCBI | |
Zibrova D, Vandermoere F, Göransson O, Peggie M, Mariño KV, Knierim A, Spengler K, Weigert C, Viollet B, Morrice NA, et al: GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis. Biochem J. 474:983–1001. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gélinas R, Mailleux F, Dontaine J, Bultot L, Demeulder B, Ginion A, Daskalopoulos EP, Esfahani H, Dubois-Deruy E, Lauzier B, et al: AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation. Nat Commun. 9:3742018. View Article : Google Scholar : PubMed/NCBI | |
Phoomak C, Vaeteewoottacharn K, Sawanyawisuth K, Seubwai W, Wongkham C, Silsirivanit A and Wongkham S: Mechanistic insights of O-GlcNAcylation that promote progression of cholangiocarcinoma cells via nuclear translocation of NF-κB. Sci Rep. 6:278532016. View Article : Google Scholar : PubMed/NCBI | |
Phoomak C, Vaeteewoottacharn K, Silsirivanit A, Saengboonmee C, Seubwai W, Sawanyawisuth K, Wongkham C and Wongkham S: High glucose levels boost the aggressiveness of highly metastatic cholangiocarcinoma cells via O-GlcNAcylation. Sci Rep. 7:438422017. View Article : Google Scholar : PubMed/NCBI | |
Jiang M, Xu B, Li X, Shang Y, Chu Y, Wang W, Chen D, Wu N, Hu S, Zhang S, et al: O-GlcNAcylation promotes colorectal cancer metastasis via the miR-101-O-GlcNAc/EZH2 regulatory feedback circuit. Oncogene. 38:301–316. 2019. View Article : Google Scholar : PubMed/NCBI | |
Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI | |
Itkonen HM, Gorad SS, Duveau DY, Martin SE, Barkovskaya A, Bathen TF, Moestue SA and Mills IG: Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism. Oncotarget. 7:12464–12476. 2016. View Article : Google Scholar : PubMed/NCBI | |
Nie H, Ju H, Fan J, Shi X, Cheng Y, Cang X, Zheng Z, Duan X and Yi W: O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth. Nat Commun. 11:362020. View Article : Google Scholar : PubMed/NCBI | |
Singh JP, Qian K, Lee JS, Zhou J, Han X, Zhang B, Ong Q, Ni W, Jiang M, Ruan HB, et al: O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene. 39:560–573. 2020. View Article : Google Scholar : PubMed/NCBI | |
Wu MJ, Shi L, Merritt J, Zhu AX and Bardeesy N: Biology of IDH mutant cholangiocarcinoma. Hepatology. 75:1322–1337. 2022. View Article : Google Scholar : PubMed/NCBI | |
He X, Wu N, Li R, Zhang H, Zhao Y, Nie Y and Wu J: IDH2, a novel target of OGT, facilitates glucose uptake and cellular bioenergy production via NF-κB signaling to promote colorectal cancer progression. Cell Oncol (Dordr). 46:145–164. 2023. View Article : Google Scholar : PubMed/NCBI | |
Rao X, Duan X, Mao W, Li X, Li Z, Li Q, Zheng Z, Xu H, Chen M, Wang PG, et al: O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nat Commun. 6:84682015. View Article : Google Scholar : PubMed/NCBI | |
Yi W, Clark PM, Mason DE, Keenan MC, Hill C, Goddard WA III, Peters EC, Driggers EM and Hsieh-Wilson LC: Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science. 337:975–980. 2012. View Article : Google Scholar : PubMed/NCBI | |
Cheng C, Geng F, Cheng X and Guo D: Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun (Lond). 38:272018.PubMed/NCBI | |
Koundouros N and Poulogiannis G: Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 122:4–22. 2020. View Article : Google Scholar : PubMed/NCBI | |
Sodi VL, Bacigalupa ZA, Ferrer CM, Lee JV, Gocal WA, Mukhopadhyay D, Wellen KE, Ivan M and Reginato MJ: Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation. Oncogene. 37:924–934. 2018. View Article : Google Scholar : PubMed/NCBI | |
Tan W, Jiang P, Zhang W, Hu Z, Lin S, Chen L, Li Y, Peng C, Li Z, Sun A, et al: Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation. Mol Cell. 81:1890–1904.e7. 2021. View Article : Google Scholar : PubMed/NCBI | |
Miller DM, Thomas SD, Islam A, Muench D and Sedoris K: c-Myc and cancer metabolism. Clin Cancer Res. 18:5546–5553. 2012. View Article : Google Scholar : PubMed/NCBI | |
Llombart V and Mansour MR: Therapeutic targeting of ‘undruggable’ MYC. EBioMedicine. 75:1037562022. View Article : Google Scholar : PubMed/NCBI | |
Morrish F, Isern N, Sadilek M, Jeffrey M and Hockenbery DM: c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry. Oncogene. 28:2485–2491. 2009. View Article : Google Scholar : PubMed/NCBI | |
Itkonen HM, Minner S, Guldvik IJ, Sandmann MJ, Tsourlakis MC, Berge V, Svindland A, Schlomm T and Mills IG: O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells. Cancer Res. 73:5277–5287. 2013. View Article : Google Scholar : PubMed/NCBI | |
Luanpitpong S, Angsutararux P, Samart P, Chanthra N, Chanvorachote P and Issaragrisil S: Hyper-O-GlcNAcylation induces cisplatin resistance via regulation of p53 and c-Myc in human lung carcinoma. Sci Rep. 7:106072017. View Article : Google Scholar : PubMed/NCBI | |
Aishima S, Fujita N, Mano Y, Kubo Y, Tanaka Y, Taketomi A, Shirabe K, Maehara Y and Oda Y: Different roles of S100P overexpression in intrahepatic cholangiocarcinoma: Carcinogenesis of perihilar type and aggressive behavior of peripheral type. Am J Surg Pathol. 35:590–598. 2011. View Article : Google Scholar : PubMed/NCBI | |
Chen T, Ruan Y, Ji L, Cai J, Tong M, Xue Y, Zhao H, Cai X and Xu J: S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway. Cancer Lett. 587:2167092024. View Article : Google Scholar : PubMed/NCBI | |
Su Y, Luo Y, Zhang P, Lin H, Pu W, Zhang H, Wang H, Hao Y, Xiao Y, Zhang X, et al: Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis. Mol Cell. 83:2316–2331.e7. 2023. View Article : Google Scholar : PubMed/NCBI | |
Song P, Gao Z, Bao Y, Chen L, Huang Y, Liu Y, Dong Q and Wei X: Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy. J Hematol Oncol. 17:462024. View Article : Google Scholar : PubMed/NCBI | |
Raab S, Gadault A, Very N, Decourcelle A, Baldini S, Schulz C, Mortuaire M, Lemaire Q, Hardivillé S, Dehennaut V, et al: Dual regulation of fatty acid synthase (FASN) expression by O-GlcNAc transferase (OGT) and mTOR pathway in proliferating liver cancer cells. Cell Mol Life Sci. 78:5397–5413. 2021. View Article : Google Scholar : PubMed/NCBI | |
Wang D, Chen D, Liang L and Hu J: The circZEB1/miR-337-3p/OGT axis mediates angiogenesis and metastasis via O-GlcNAcylation and up-regulating YBX1 in breast cancer. Heliyon. 10:e340792024. View Article : Google Scholar : PubMed/NCBI | |
Babae N, Bourajjaj M, Liu Y, Van Beijnum JR, Cerisoli F, Scaria PV, Verheul M, Van Berkel MP, Pieters EH, Van Haastert RJ, et al: Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma. Oncotarget. 5:6687–6700. 2014. View Article : Google Scholar : PubMed/NCBI | |
Weis SM and Cheresh DA: Tumor angiogenesis: Molecular pathways and therapeutic targets. Nat Med. 17:1359–1370. 2011. View Article : Google Scholar : PubMed/NCBI | |
Lynch TP, Ferrer CM, Jackson SR, Shahriari KS, Vosseller K and Reginato MJ: Critical role of O-linked β-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis. J Biol Chem. 287:11070–11081. 2012. View Article : Google Scholar : PubMed/NCBI | |
Zhu Q, Zhou L, Yang Z, Lai M, Xie H, Wu L, Xing C, Zhang F and Zheng S: O-GlcNAcylation plays a role in tumor recurrence of hepatocellular carcinoma following liver transplantation. Med Oncol. 29:985–993. 2012. View Article : Google Scholar : PubMed/NCBI | |
Duan F, Wu H, Jia D, Wu W, Ren S, Wang L, Song S, Guo X, Liu F, Ruan Y and Gu J: O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis. J Hepatol. 68:1191–1202. 2018. View Article : Google Scholar : PubMed/NCBI | |
Luo B, Soesanto Y and McClain DA: Protein modification by O-linked GlcNAc reduces angiogenesis by inhibiting Akt activity in endothelial cells. Arterioscler Thromb Vasc Biol. 28:651–657. 2008. View Article : Google Scholar : PubMed/NCBI | |
Li X, Peng X, Zhang C, Bai X, Li Y, Chen G, Guo H, He W, Zhou X and Gou X: Bladder cancer-derived small extracellular vesicles promote tumor angiogenesis by inducing HBP-related metabolic reprogramming and SerRS O-GlcNAcylation in endothelial cells. Adv Sci (Weinh). 9:e22029932022. View Article : Google Scholar : PubMed/NCBI | |
Hanahan D: Hallmarks of cancer: New dimensions. Cancer Discov. 12:31–46. 2022. View Article : Google Scholar : PubMed/NCBI | |
Shen S, Shao Y and Li C: Different types of cell death and their shift in shaping disease. Cell Death Discov. 9:2842023. View Article : Google Scholar : PubMed/NCBI | |
Scimeca M, Rovella V, Palumbo V, Scioli MP, Bonfiglio R, Tor Centre, Melino G, Piacentini M, Frati L, Agostini M, et al: Programmed cell death pathways in cholangiocarcinoma: Opportunities for targeted therapy. Cancers (Basel). 15:36382023. View Article : Google Scholar : PubMed/NCBI | |
D'Artista L and Seehawer M: Cell Death and survival mechanisms in cholangiocarcinogenesis. Am J Pathol. 195:470–479. 2025. View Article : Google Scholar : PubMed/NCBI | |
Li M, Duan F, Pan Z, Liu X, Lu W, Liang C, Fang Z, Peng P and Jia D: Astragalus polysaccharide promotes doxorubicin-induced apoptosis by reducing O-GlcNAcylation in hepatocellular carcinoma. Cells. 12:8662023. View Article : Google Scholar : PubMed/NCBI | |
Barkovskaya A, Seip K, Prasmickaite L, Mills IG, Moestue SA and Itkonen HM: Inhibition of O-GlcNAc transferase activates tumor-suppressor gene expression in tamoxifen-resistant breast cancer cells. Sci Rep. 10:169922020. View Article : Google Scholar : PubMed/NCBI | |
Wu J, Tan Z, Li H, Lin M, Jiang Y, Liang L, Ma Q, Gou J, Ning L, Li X and Guan F: Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O-GlcNAcylation of cyclin-dependent-like kinase 5. J Pineal Res. 71:e127652021. View Article : Google Scholar : PubMed/NCBI | |
Deng X, Yi X, Huang D, Liu P, Chen L, Du Y and Hao L: ROCK2 mediates osteosarcoma progression and TRAIL resistance by modulating O-GlcNAc transferase degradation. Am J Cancer Res. 10:781–798. 2020.PubMed/NCBI | |
Wang L, Chen S, Zhang Z, Zhang J, Mao S, Zheng J, Xuan Y, Liu M, Cai K, Zhang W, et al: Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer. BMC Cancer. 18:11412018. View Article : Google Scholar : PubMed/NCBI | |
Yu FY, Zhou CY, Liu YB, Wang B, Mao L and Li Y: miR-483 is down-regulated in gastric cancer and suppresses cell proliferation, invasion and protein O-GlcNAcylation by targeting OGT. Neoplasma. 65:406–414. 2018. View Article : Google Scholar : PubMed/NCBI | |
Wen T, Hou K, Li Z, Li L, Yu H, Liu Y, Li Y and Yin Z: Silencing β-linked N-acetylglucosamine transferase induces apoptosis in human gastric cancer cells through PUMA and caspase-3 pathways. Oncol Rep. 34:3140–3146. 2015. View Article : Google Scholar : PubMed/NCBI | |
Asthana A, Ramakrishnan P, Vicioso Y, Zhang K and Parameswaran R: Hexosamine biosynthetic pathway inhibition leads to AML cell differentiation and cell death. Mol Cancer Ther. 17:2226–2237. 2018. View Article : Google Scholar : PubMed/NCBI | |
Lee SJ, Lee DE, Choi SY and Kwon OS: OSMI-1 enhances TRAIL-induced apoptosis through ER stress and NF-κB signaling in colon cancer cells. Int J Mol Sci. 22:110732021. View Article : Google Scholar : PubMed/NCBI | |
Ferrer CM, Lynch TP, Sodi VL, Falcone JN, Schwab LP, Peacock DL, Vocadlo DJ, Seagroves TN and Reginato MJ: O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway. Mol Cell. 54:820–831. 2014. View Article : Google Scholar : PubMed/NCBI | |
Loison I, Pioger A, Paget S, Metatla I; OrgaRES Consortium, ; Vincent A, Abbadie C and Dehennaut V: O-GlcNAcylation inhibition redirects the response of colon cancer cells to chemotherapy from senescence to apoptosis. Cell Death Dis. 15:7622024. View Article : Google Scholar : PubMed/NCBI | |
Leonel AV, Alisson-Silva F, Santos RCM, Silva-Aguiar RP, Gomes JC, Longo GMC, Faria BM, Siqueira MS, Pereira MG, Vasconcelos-Dos-Santos A, et al: Inhibition of O-GlcNAcylation reduces cell viability and autophagy and increases sensitivity to chemotherapeutic temozolomide in glioblastoma. Cancers (Basel). 15:47402023. View Article : Google Scholar : PubMed/NCBI | |
Ben Ahmed A, Scache J, Mortuaire M, Lefebvre T and Vercoutter-Edouart AS: Downregulation of O-GlcNAc transferase activity impairs basal autophagy and late endosome positioning under nutrient-rich conditions in human colon cells. Biochem Biophys Res Commun. 724:1501982024. View Article : Google Scholar : PubMed/NCBI | |
Zhu Y, Shan X, Safarpour F, Erro Go N, Li N, Shan A, Huang MC, Deen M, Holicek V, Ashmus R, et al: Pharmacological inhibition of O-GlcNAcase enhances autophagy in brain through an mTOR-independent pathway. ACS Chem Neurosci. 9:1366–1379. 2018. View Article : Google Scholar : PubMed/NCBI | |
Jo YK, Park NY, Park SJ, Kim BG, Shin JH, Jo DS, Bae DJ, Suh YA, Chang JH, Lee EK, et al: O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity. Oncotarget. 7:57186–57196. 2016. View Article : Google Scholar : PubMed/NCBI | |
Shi Y, Yan S, Shao GC, Wang J, Jian YP, Liu B, Yuan Y, Qin K, Nai S, Huang X, et al: O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection. J Biol Chem. 298:1023412022. View Article : Google Scholar : PubMed/NCBI | |
Sun QH, Wang YS, Liu G, Zhou HL, Jian YP, Liu MD, Zhang D, Ding Q, Zhao RX, Chen JF, et al: Enhanced O-linked glcnacylation in Crohn's disease promotes intestinal inflammation. EBioMedicine. 53:1026932020. View Article : Google Scholar : PubMed/NCBI | |
Guo B, Liang Q, Li L, Hu Z, Wu F, Zhang P, Ma Y, Zhao B, Kovács AL, Zhang Z, et al: O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nat Cell Biol. 16:1215–1226. 2014. View Article : Google Scholar : PubMed/NCBI | |
Pellegrini FR, De Martino S, Fianco G, Ventura I, Valente D, Fiore M, Trisciuoglio D and Degrassi F: Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production. Autophagy. 19:2078–2093. 2023. View Article : Google Scholar : PubMed/NCBI | |
Zhou F, Yang X, Zhao H, Liu Y, Feng Y, An R, Lv X, Li J and Chen B: Down-regulation of OGT promotes cisplatin resistance by inducing autophagy in ovarian cancer. Theranostics. 8:5200–5212. 2018. View Article : Google Scholar : PubMed/NCBI | |
Ruan HB, Ma Y, Torres S, Zhang B, Feriod C, Heck RM, Qian K, Fu M, Li X, Nathanson MH, et al: Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation. Genes Dev. 31:1655–1665. 2017. View Article : Google Scholar : PubMed/NCBI | |
Zhang H, Zhang J, Dong H, Kong Y and Guan Y: Emerging field: O-GlcNAcylation in ferroptosis. Front Mol Biosci. 10:12032692023. View Article : Google Scholar : PubMed/NCBI | |
Tang J, Long G, Hu K, Xiao D, Liu S, Xiao L, Zhou L and Tao Y: Targeting USP8 inhibits O-GlcNAcylation of SLC7A11 to promote ferroptosis of hepatocellular carcinoma via stabilization of OGT. Adv Sci (Weinh). 10:e23029532023. View Article : Google Scholar : PubMed/NCBI | |
Liu H, Fu Y, Tang L, Song B, Gu W, Yang H, Xiao T, Wang H and Chen P: O-GlcNAc-modified HOXA9 suppresses ferroptosis via promoting UBR5-mediated SIRT6 degradation in nasopharyngeal carcinoma. Neoplasia. 62:1011422025. View Article : Google Scholar : PubMed/NCBI | |
Li Q, Cheng Y, Yang C, Tian M, Wang X, Li D, Li X, Qu J, Zhou S, Zheng L and Tong Q: Targeting the exonic circular OGT RNA/O-GlcNAc transferase/forkhead box C1 axis inhibits asparagine- and alanine-mediated ferroptosis repression in neuroblastoma progression. Research (Wash D C). 8:07032025.PubMed/NCBI | |
Yang Z, Wei X, Ji C, Ren X, Su W, Wang Y, Zhou J, Zhao Z, Zhou P, Zhao K, et al: OGT/HIF-2α axis promotes the progression of clear cell renal cell carcinoma and regulates its sensitivity to ferroptosis. iScience. 26:1081482023. View Article : Google Scholar : PubMed/NCBI | |
Li X, Gong W, Wang H, Li T, Attri KS, Lewis RE, Kalil AC, Bhinderwala F, Powers R, Yin G, et al: O-GlcNAc transferase suppresses inflammation and necroptosis by targeting receptor-interacting serine/threonine-protein kinase 3. Immunity. 50:576–590.e6. 2019. View Article : Google Scholar : PubMed/NCBI | |
Zhang B, Li MD, Yin R, Liu Y, Yang Y, Mitchell-Richards KA, Nam JH, Li R, Wang L, Iwakiri Y, et al: O-GlcNAc transferase suppresses necroptosis and liver fibrosis. JCI Insight. 4:e1277092019. View Article : Google Scholar : PubMed/NCBI | |
Brindley PJ, Bachini M, Ilyas SI, Khan SA, Loukas A, Sirica AE, Teh BT, Wongkham S and Gores GJ: Cholangiocarcinoma. Nat Rev Dis Primers. 7:652021. View Article : Google Scholar : PubMed/NCBI | |
Labib PL, Goodchild G and Pereira SP: Molecular pathogenesis of cholangiocarcinoma. BMC Cancer. 19:1852019. View Article : Google Scholar : PubMed/NCBI | |
Leone V, Ali A, Weber A, Tschaharganeh DF and Heikenwalder M: Liver inflammation and hepatobiliary cancers. Trends Cancer. 7:606–623. 2021. View Article : Google Scholar : PubMed/NCBI | |
Ouyang M, Yu C, Deng X, Zhang Y, Zhang X and Duan F: O-GlcNAcylation and its role in cancer-associated inflammation. Front Immunol. 13:8615592022. View Article : Google Scholar : PubMed/NCBI | |
Yang WH, Park SY, Nam HW, Kim DH, Kang JG, Kang ES, Kim YS, Lee HC, Kim KS and Cho JW: NFkappaB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions. Proc Natl Acad Sci USA. 105:17345–17350. 2008. View Article : Google Scholar : PubMed/NCBI | |
Ali A, Kim SH, Kim MJ, Choi MY, Kang SS, Cho GJ, Kim YS, Choi JY and Choi WS: O-GlcNAcylation of NF-κB promotes lung metastasis of cervical cancer cells via upregulation of CXCR4 expression. Mol Cells. 40:476–484. 2017. View Article : Google Scholar : PubMed/NCBI | |
Yang YR, Kim DH, Seo YK, Park D, Jang HJ, Choi SY, Lee YH, Lee GH, Nakajima K, Taniguchi N, et al: Elevated O-GlcNAcylation promotes colonic inflammation and tumorigenesis by modulating NF-κB signaling. Oncotarget. 6:12529–12542. 2015. View Article : Google Scholar : PubMed/NCBI | |
Pathak S, Borodkin VS, Albarbarawi O, Campbell DG, Ibrahim A and van Aalten DM: O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO J. 31:1394–1404. 2012. View Article : Google Scholar : PubMed/NCBI | |
Kawauchi K, Araki K, Tobiume K and Tanaka N: Loss of p53 enhances catalytic activity of IKKbeta through O-linked beta-N-acetyl glucosamine modification. Proc Natl Acad Sci USA. 106:3431–3436. 2009. View Article : Google Scholar : PubMed/NCBI | |
Li X, Zhang Z, Li L, Gong W, Lazenby AJ, Swanson BJ, Herring LE, Asara JM, Singer JD and Wen H: Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. J Exp Med. 214:1093–1109. 2017. View Article : Google Scholar : PubMed/NCBI | |
Freund P, Kerenyi MA, Hager M, Wagner T, Wingelhofer B, Pham HTT, Elabd M, Han X, Valent P, Gouilleux F, et al: O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies. Leukemia. 31:2132–2142. 2017. View Article : Google Scholar : PubMed/NCBI | |
Jin H, He H, Li J, Liu X, Cai Q, Shi J, Hao Z and He J: Mannose Inhibits NSCLC growth and inflammatory microenvironment by regulating gut microbiota and targeting OGT/hnRNP R/JUN/IL-8 axis. Int J Biol Sci. 21:1566–1584. 2025. View Article : Google Scholar : PubMed/NCBI | |
Hinshaw DC, Hanna A, Lama-Sherpa T, Metge B, Kammerud SC, Benavides GA, Kumar A, Alsheikh HA, Mota M, Chen D, et al: Hedgehog signaling regulates metabolism and polarization of mammary tumor-associated macrophages. Cancer Res. 81:5425–5437. 2021. View Article : Google Scholar : PubMed/NCBI | |
Hinshaw DC, Benavides GA, Metge BJ, Swain CA, Kammerud SC, Alsheikh HA, Elhamamsy A, Chen D, Darley-Usmar V, Rathmell JC, et al: Hedgehog signaling regulates Treg to Th17 conversion through metabolic rewiring in breast cancer. Cancer Immunol Res. 11:687–702. 2023. View Article : Google Scholar : PubMed/NCBI | |
Das S, Bailey SK, Metge BJ, Hanna A, Hinshaw DC, Mota M, Forero-Torres A, Chatham JC, Samant RS and Shevde LA: O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity. Lab Invest. 99:260–270. 2019. View Article : Google Scholar : PubMed/NCBI | |
Chen L, Li Y, Song Z, Xue S, Liu F, Chang X, Wu Y, Duan X and Wu H: O-GlcNAcylation promotes cerebellum development and medulloblastoma oncogenesis via SHH signaling. Proc Natl Acad Sci USA. 119:e22028211192022. View Article : Google Scholar : PubMed/NCBI | |
Rodrigues Mantuano N, Stanczak MA, Oliveira IA, Kirchhammer N, Filardy AA, Monaco G, Santos RC, Fonseca AC, Fontes M, Bastos CS Jr, et al: Hyperglycemia enhances cancer immune evasion by inducing alternative macrophage polarization through increased O-GlcNAcylation. Cancer Immunol Res. 8:1262–1272. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zhang HR, Li TJ, Yu XJ, Liu C, Wu WD, Ye LY and Jin KZ: The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer. Cell Death Dis. 15:2442024. View Article : Google Scholar : PubMed/NCBI | |
Shi Q, Shen Q, Liu Y, Shi Y, Huang W, Wang X, Li Z, Chai Y, Wang H, Hu X, et al: Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal cathepsin B to promote cancer metastasis and chemoresistance. Cancer Cell. 40:1207–1222.e10. 2022. View Article : Google Scholar : PubMed/NCBI | |
Alsheikh HAM, Metge BJ, Ha CM, Hinshaw DC, Mota MSV, Kammerud SC, Lama-Sherpa T, Sharafeldin N, Wende AR, Samant RS and Shevde LA: Normalizing glucose levels reconfigures the mammary tumor immune and metabolic microenvironment and decreases metastatic seeding. Cancer Lett. 517:24–34. 2021. View Article : Google Scholar : PubMed/NCBI | |
Swamy M, Pathak S, Grzes KM, Damerow S, Sinclair LV, van Aalten DM and Cantrell DA: Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. Nat Immunol. 17:712–720. 2016. View Article : Google Scholar : PubMed/NCBI | |
Lopez Aguilar A, Gao Y, Hou X, Lauvau G, Yates JR and Wu P: Profiling of protein O-GlcNAcylation in murine CD8+ effector- and memory-like T cells. ACS Chem Biol. 12:3031–3038. 2017. View Article : Google Scholar : PubMed/NCBI | |
Qiu Y, Su Y, Xie E, Cheng H, Du J, Xu Y, Pan X, Wang Z, Chen DG, Zhu H, et al: Mannose metabolism reshapes T cell differentiation to enhance anti-tumor immunity. Cancer Cell. 43:103–121.e8. 2025. View Article : Google Scholar : PubMed/NCBI | |
Machacek M, Saunders H, Zhang Z, Tan EP, Li J, Li T, Villar MT, Artigues A, Lydic T, Cork G, et al: Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment. J Biol Chem. 294:8973–8990. 2019. View Article : Google Scholar : PubMed/NCBI | |
Liu B, Salgado OC, Singh S, Hippen KL, Maynard JC, Burlingame AL, Ball LE, Blazar BR, Farrar MA, Hogquist KA and Ruan HB: The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation. Nat Commun. 10:3542019. View Article : Google Scholar : PubMed/NCBI | |
Yuan Y, Wang L, Ge D, Tan L, Cao B, Fan H and Xue L: Exosomal O-GlcNAc transferase from esophageal carcinoma stem cell promotes cancer immunosuppression through up-regulation of PD-1 in CD8+ T cells. Cancer Lett. 500:98–106. 2021. View Article : Google Scholar : PubMed/NCBI | |
Perišić Nanut M, Pečar Fonović U, Jakoš T and Kos J: The role of cysteine peptidases in hematopoietic stem cell differentiation and modulation of immune system function. Front Immunol. 12:6802792021. View Article : Google Scholar : PubMed/NCBI | |
Božič J, Stoka V and Dolenc I: Glucosamine prevents polarization of cytotoxic granules in NK-92 cells by disturbing FOXO1/ERK/paxillin phosphorylation. PLoS One. 13:e02007572018. View Article : Google Scholar : PubMed/NCBI | |
Zhang N, Jiang H, Zhang K, Zhu J, Wang Z, Long Y, He Y, Feng F, Liu W, Ye F and Qu W: OGT as potential novel target: Structure, function and inhibitors. Chem Biol Interact. 357:1098862022. View Article : Google Scholar : PubMed/NCBI | |
Konrad RJ, Zhang F, Hale JE, Knierman MD, Becker GW and Kudlow JE: Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase. Biochem Biophys Res Commun. 293:207–212. 2002. View Article : Google Scholar : PubMed/NCBI | |
Liu TW, Zandberg WF, Gloster TM, Deng L, Murray KD, Shan X and Vocadlo DJ: Metabolic inhibitors of O-GlcNAc transferase that act in vivo implicate decreased O-GlcNAc levels in leptin-mediated nutrient sensing. Angew Chem Int Ed Engl. 57:7644–7648. 2018. View Article : Google Scholar : PubMed/NCBI | |
Pantaleon M, Tan HY, Kafer GR and Kaye PL: Toxic effects of hyperglycemia are mediated by the hexosamine signaling pathway and o-linked glycosylation in early mouse embryos. Biol Reprod. 82:751–758. 2010. View Article : Google Scholar : PubMed/NCBI | |
Gross BJ, Kraybill BC and Walker S: Discovery of O-GlcNAc transferase inhibitors. J Am Chem Soc. 127:14588–14589. 2005. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Ren Y, Cao Y, Huang H, Wu Q, Li W, Wu S and Zhang J: Discovery of a low toxicity O-GlcNAc transferase (OGT) inhibitor by structure-based virtual screening of natural products. Sci Rep. 7:123342017. View Article : Google Scholar : PubMed/NCBI | |
Ortiz-Meoz RF, Jiang J, Lazarus MB, Orman M, Janetzko J, Fan C, Duveau DY, Tan ZW, Thomas CJ and Walker S: A small molecule that inhibits OGT activity in cells. ACS Chem Biol. 10:1392–1397. 2015. View Article : Google Scholar : PubMed/NCBI | |
Martin SES, Tan ZW, Itkonen HM, Duveau DY, Paulo JA, Janetzko J, Boutz PL, Törk L, Moss FA, Thomas CJ, et al: Structure-based evolution of low nanomolar O-GlcNAc transferase inhibitors. J Am Chem Soc. 140:13542–13545. 2018. View Article : Google Scholar : PubMed/NCBI | |
Efimova EV, Appelbe OK, Ricco N, Lee SS, Liu Y, Wolfgeher DJ, Collins TN, Flor AC, Ramamurthy A, Warrington S, et al: O-GlcNAcylation enhances double-strand break repair, promotes cancer cell proliferation, and prevents therapy-induced senescence in irradiated tumors. Mol Cancer Res. 17:1338–1350. 2019. View Article : Google Scholar : PubMed/NCBI | |
Huang YJ, Chen YT, Huang CM, Kuo SH, Liao YY, Jhang WY, Wang SH, Ke CC, Huang YH, Cheng CM, et al: HIF-1α expression increases preoperative concurrent chemoradiotherapy resistance in hyperglycemic rectal cancer. Cancers (Basel). 14:40532022. View Article : Google Scholar : PubMed/NCBI | |
Ping X and Stark JM: O-GlcNAc transferase is important for homology-directed repair. DNA Repair (Amst). 119:1033942022. View Article : Google Scholar : PubMed/NCBI | |
Na HJ, Akan I, Abramowitz LK and Hanover JA: Nutrient-driven O-GlcNAcylation controls DNA damage repair signaling and stem/progenitor cell homeostasis. Cell Rep. 31:1076322020. View Article : Google Scholar : PubMed/NCBI | |
Naimi A, Mohammed RN, Raji A, Chupradit S, Yumashev AV, Suksatan W, Shalaby MN, Thangavelu L, Kamrava S, Shomali N, et al: Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons. Cell Commun Signal. 20:442022. View Article : Google Scholar : PubMed/NCBI | |
Zhu Q, Wang H, Chai S, Xu L, Lin B, Yi W and Wu L: O-GlcNAcylation promotes tumor immune evasion by inhibiting PD-L1 lysosomal degradation. Proc Natl Acad Sci USA. 120:e22167961202023. View Article : Google Scholar : PubMed/NCBI | |
Chen J, Zhao B, Dong H, Li T, Cheng X, Gong W, Wang J, Zhang J, Xin G, Yu Y, et al: Inhibition of O-GlcNAc transferase activates type I interferon-dependent antitumor immunity by bridging cGAS-STING pathway. Elife. 13:RP948492024. View Article : Google Scholar : PubMed/NCBI | |
Kumatori A, Tanaka K, Inamura N, Sone S, Ogura T, Matsumoto T, Tachikawa T, Shin S and Ichihara A: Abnormally high expression of proteasomes in human leukemic cells. Proc Natl Acad Sci USA. 87:7071–7075. 1990. View Article : Google Scholar : PubMed/NCBI | |
Chen L and Madura K: Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer Res. 65:5599–5606. 2005. View Article : Google Scholar : PubMed/NCBI | |
Arlt A, Bauer I, Schafmayer C, Tepel J, Müerköster SS, Brosch M, Röder C, Kalthoff H, Hampe J, Moyer MP, et al: Increased proteasome subunit protein expression and proteasome activity in colon cancer relate to an enhanced activation of nuclear factor E2-related factor 2 (Nrf2). Oncogene. 28:3983–3996. 2009. View Article : Google Scholar : PubMed/NCBI | |
Soave CL, Guerin T, Liu J and Dou QP: Targeting the ubiquitin-proteasome system for cancer treatment: Discovering novel inhibitors from nature and drug repurposing. Cancer Metastasis Rev. 36:717–736. 2017. View Article : Google Scholar : PubMed/NCBI | |
Fricker LD: Proteasome inhibitor drugs. Annu Rev Pharmacol Toxicol. 60:457–476. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zhang F, Su K, Yang X, Bowe DB, Paterson AJ and Kudlow JE: O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell. 115:715–725. 2003. View Article : Google Scholar : PubMed/NCBI | |
Sekine H, Okazaki K, Kato K, Alam MM, Shima H, Katsuoka F, Tsujita T, Suzuki N, Kobayashi A, Igarashi K, et al: O-GlcNAcylation signal mediates proteasome inhibitor resistance in cancer cells by stabilizing NRF1. Mol Cell Biol. 38:e00252–18. 2018. View Article : Google Scholar : PubMed/NCBI | |
Hashimoto E, Okuno S, Hirayama S, Arata Y, Goto T, Kosako H, Hamazaki J and Murata S: Enhanced O-GlcNAcylation mediates cytoprotection under proteasome impairment by promoting proteasome turnover in cancer cells. iScience. 23:1012992020. View Article : Google Scholar : PubMed/NCBI | |
Zeidan Q, Tian JL, Ma J, Eslami F and Hart GW: O-GlcNAcylation of ribosome-associated proteins is concomitant with translational reprogramming during proteotoxic stress. J Biol Chem. 300:1078772024. View Article : Google Scholar : PubMed/NCBI | |
Xia M, Wang S, Qi Y, Long K, Li E, He L, Pan F, Guo Z and Hu Z: Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel. Front Oncol. 12:9932432022. View Article : Google Scholar : PubMed/NCBI | |
Sun MX, An HY, Sun YB, Sun YB and Bai B: LncRNA EBLN3P attributes methotrexate resistance in osteosarcoma cells through miR-200a-3p/O-GlcNAc transferase pathway. J Orthop Surg Res. 17:5572022. View Article : Google Scholar : PubMed/NCBI | |
Kwei KA, Baker JB and Pelham RJ: Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection. PLoS One. 7:e465182012. View Article : Google Scholar : PubMed/NCBI | |
Wongprayoon P, Pengnam S, Srisuphan R, Opanasopit P, Jirawatnotai S and Charoensuksai P: The correlation between cellular O-GlcNAcylation and sensitivity to O-GlcNAc inhibitor in colorectal cancer cells. PLoS One. 19:e03121732024. View Article : Google Scholar : PubMed/NCBI | |
Pallasaho S, Gondane A, Kuivalainen A, Girmay S, Moestue S, Loda M and Itkonen HM: Castration-resistant prostate cancer cells are dependent on the high activity of CDK7. J Cancer Res Clin Oncol. 149:5255–5263. 2023. View Article : Google Scholar : PubMed/NCBI | |
Itkonen HM, Poulose N, Steele RE, Martin SES, Levine ZG, Duveau DY, Carelli R, Singh R, Urbanucci A, Loda M, et al: Inhibition of O-GlcNAc transferase renders prostate cancer cells dependent on CDK9. Mol Cancer Res. 18:1512–1521. 2020. View Article : Google Scholar : PubMed/NCBI | |
Shan X, Jiang R, Gou D, Xiang J, Zhou P, Xia J, Wang K, Huang A, Tang N and Huang L: Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition. FEBS J. 290:4543–4561. 2023. View Article : Google Scholar : PubMed/NCBI | |
Areewong S, Suppramote O, Prasopporn S and Jirawatnotai S: Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma. Cancer Cell Int. 24:3622024. View Article : Google Scholar : PubMed/NCBI | |
Carlson GP: Potentiation of carbon tetrachloride hepatotoxicity in rats by pretreatment with polychlorinated biphenyls. Toxicology. 5:69–77. 1975. View Article : Google Scholar : PubMed/NCBI | |
Dong W, Zhu Q, Yang B, Qin Q, Wang Y, Xia X, Zhu X, Liu Z, Song E and Song Y: Polychlorinated biphenyl quinone induces caspase 1-mediated pyroptosis through induction of pro-inflammatory HMGB1-TLR4-NLRP3-GSDMD signal axis. Chem Res Toxicol. 32:1051–1057. 2019. View Article : Google Scholar : PubMed/NCBI | |
Brown AP, Schultze AE, Holdan WL, Buchweitz JP, Roth RA and Ganey PE: Lipopolysaccharide-induced hepatic injury is enhanced by polychlorinated biphenyls. Environ Health Perspect. 104:634–640. 1996. View Article : Google Scholar : PubMed/NCBI | |
National Toxicology Program, . Toxicology and carcinogenesis studies of 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118) (CAS No. 31508-00-6) in female harlan Sprague-Dawley rats (gavage studies). Natl Toxicol Program Tech Rep Ser. 1–174. 2010. | |
National Toxicology Program, . NTP toxicology and carcinogenesis studies of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (Gavage Studies). Natl Toxicol Program Tech Rep Ser. 4–246. 2006. | |
Ovando BJ, Ellison CA, Vezina CM and Olson JR: Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: Identification of genomic biomarkers of exposure to AhR ligands. BMC Genomics. 11:5832010. View Article : Google Scholar : PubMed/NCBI |