Open Access

Notch3 mediated TGF‑β1 activation enhances epithelial‑mesenchymal transition and cancer stemness in non‑small lung cancer

  • Authors:
    • Fang Wang
    • Siqi Hu
    • Jiangrong Bian
    • Qing Gao
    • Liuzhao Cao
    • Linli Sang
    • Junjun Yang
    • Xingxiang Xu
  • View Affiliations

  • Published online on: August 20, 2025     https://doi.org/10.3892/ijo.2025.5791
  • Article Number: 85
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Notch3 is a key regulator in various cancers, playing a crucial role in maintaining stemness and promoting epithelial‑mesenchymal transition (EMT). However, its differential expression and regulatory mechanisms in non‑small cell lung cancer (NSCLC) and cancer stem cells remain poorly understood. To investigate this, the present study examined Notch3 expression in NSCLC through Oncomine, The Cancer Genome Atlas and Gene Expression Omnibus databases and validated the results with immunohistochemistry, reverse transcription‑quantitative PCR and western blotting. EMT was induced by TGF‑β1 in NSCLC cells and functional assays (Transwell, wound healing and sphere formation) were performed to assess cellular changes. In vivo experiments using a xenograft mouse model were conducted to evaluate tumor growth and metastasis. The results showed that high Notch3 expression was associated with poor prognosis in NSCLC patients. Downregulation of Notch3 inhibited TGF‑β1‑induced EMT and CSC characteristics, resulting in reduced tumorigenic potential, whereas overexpression of the Notch3 intracellular domain enhanced these effects. Silencing Notch3 suppressed EMT and markedly inhibited tumor growth and metastasis in vivo. These findings demonstrated that Notch3 regulated EMT and CSC properties in NSCLC, promoting tumor recurrence and metastasis. Notch3 thus represents a promising therapeutic target and prognostic marker for NSCLC.
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October-2025
Volume 67 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wang F, Hu S, Bian J, Gao Q, Cao L, Sang L, Yang J and Xu X: Notch3 mediated TGF‑β1 activation enhances epithelial‑mesenchymal transition and cancer stemness in non‑small lung cancer. Int J Oncol 67: 85, 2025.
APA
Wang, F., Hu, S., Bian, J., Gao, Q., Cao, L., Sang, L. ... Xu, X. (2025). Notch3 mediated TGF‑β1 activation enhances epithelial‑mesenchymal transition and cancer stemness in non‑small lung cancer. International Journal of Oncology, 67, 85. https://doi.org/10.3892/ijo.2025.5791
MLA
Wang, F., Hu, S., Bian, J., Gao, Q., Cao, L., Sang, L., Yang, J., Xu, X."Notch3 mediated TGF‑β1 activation enhances epithelial‑mesenchymal transition and cancer stemness in non‑small lung cancer". International Journal of Oncology 67.4 (2025): 85.
Chicago
Wang, F., Hu, S., Bian, J., Gao, Q., Cao, L., Sang, L., Yang, J., Xu, X."Notch3 mediated TGF‑β1 activation enhances epithelial‑mesenchymal transition and cancer stemness in non‑small lung cancer". International Journal of Oncology 67, no. 4 (2025): 85. https://doi.org/10.3892/ijo.2025.5791