Heteronemin suppresses EGF‑induced proliferation through the PI3K/PD‑L1 signaling pathways in cholangiocarcinoma

  • Authors:
    • Yu-Chen S.H. Yang
    • Chung-Che Tsai
    • Yung-Ning Yang
    • Feng-Cheng Liu
    • Sheng-Yang Lee
    • Jen-Chang Yang
    • Dana R. Crawford
    • Hsien-Chung Chiu
    • Mei-Chin Lu
    • Zi-Lin Li
    • Yi-Chen Chen
    • Tin-Yi Chu
    • Jacqueline Whang-Peng
    • Hung-Yun Lin
    • Kuan Wang
  • View Affiliations

  • Published online on: January 9, 2025     https://doi.org/10.3892/or.2025.8865
  • Article Number: 32
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Abstract

Epidermal growth factor (EGF) binds with its surface receptor to stimulate gene expression and cancer cell proliferation. EGF stimulates cancer cell growth via phosphoinositide 3‑kinase (PI3K) and programmed cell death ligand 1 (PD‑L1) pathways. As an integrin αvβ3 antagonist, heteronemin exhibits potent cytotoxic effects against cancer cells. It inhibits critical signal transduction pathways promoted by the EGF. In the current study, EGF‑induced signal activation and proliferative effects were investigated in cholangiocarcinoma cells and its molecular targets using qPCR and western blotting analyses. In addition, cell viability assays were performed to assess the growth effects of EGF and heteronemin. Heteronemin reversed the effects of EGF and was further enhanced by blockage of PI3K's activity. In summary, EGF stimulates cholangiocarcinoma cell growth. On the other hand, heteronemin inhibited PI3K activation and PD‑L1 expression to reverse the stimulative effects of EGF‑induced gene expression and proliferation in cholangiocarcinoma cells.
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March-2025
Volume 53 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yang YS, Tsai C, Yang Y, Liu F, Lee S, Yang J, Crawford DR, Chiu H, Lu M, Li Z, Li Z, et al: Heteronemin suppresses EGF‑induced proliferation through the PI3K/PD‑L1 signaling pathways in cholangiocarcinoma. Oncol Rep 53: 32, 2025.
APA
Yang, Y.S., Tsai, C., Yang, Y., Liu, F., Lee, S., Yang, J. ... Wang, K. (2025). Heteronemin suppresses EGF‑induced proliferation through the PI3K/PD‑L1 signaling pathways in cholangiocarcinoma. Oncology Reports, 53, 32. https://doi.org/10.3892/or.2025.8865
MLA
Yang, Y. S., Tsai, C., Yang, Y., Liu, F., Lee, S., Yang, J., Crawford, D. R., Chiu, H., Lu, M., Li, Z., Chen, Y., Chu, T., Whang-Peng, J., Lin, H., Wang, K."Heteronemin suppresses EGF‑induced proliferation through the PI3K/PD‑L1 signaling pathways in cholangiocarcinoma". Oncology Reports 53.3 (2025): 32.
Chicago
Yang, Y. S., Tsai, C., Yang, Y., Liu, F., Lee, S., Yang, J., Crawford, D. R., Chiu, H., Lu, M., Li, Z., Chen, Y., Chu, T., Whang-Peng, J., Lin, H., Wang, K."Heteronemin suppresses EGF‑induced proliferation through the PI3K/PD‑L1 signaling pathways in cholangiocarcinoma". Oncology Reports 53, no. 3 (2025): 32. https://doi.org/10.3892/or.2025.8865