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

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

doi:10.3892/or.2025.8865

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

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

Research output: Contribution to journal › Article › peer-review

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 antago‑ nist, 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.

Original language	English
Article number	32
Journal	Oncology Reports
Volume	53
Issue number	3
DOIs	https://doi.org/10.3892/or.2025.8865
Publication status	Published - Mar 2025

Keywords

EGF
PD‑L1
cancer immunotherapy
cholangiocarcinoma
heteronemin

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3892/or.2025.8865

Cite this

Yang, Y. C. S. H., Tsai, C. C., Yang, Y. N., Liu, F. C., Lee, S. Y., Yang, J. C., Crawford, D. R., Chiu, H. C., Lu, M. C., Li, Z. L., Chen, Y. C., Chu, T. Y., Whang-Peng, J., Lin, H. Y., & Wang, K. (2025). Heteronemin suppresses EGF‑induced proliferation through the PI3K/PD‑L1 signaling pathways in cholangiocarcinoma. Oncology Reports, 53(3), Article 32. https://doi.org/10.3892/or.2025.8865

@article{ec63a559c4794370b018143d20946448,

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

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 antago‑ nist, 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.",

keywords = "EGF, PD‑L1, cancer immunotherapy, cholangiocarcinoma, heteronemin",

author = "Yang, {Yu Chen S.H.} and Tsai, {Chung Che} and Yang, {Yung Ning} and Liu, {Feng Cheng} and Lee, {Sheng Yang} and Yang, {Jen Chang} and Crawford, {Dana R.} and Chiu, {Hsien Chung} and Lu, {Mei Chin} and Li, {Zi Lin} and Chen, {Yi Chen} and Chu, {Tin Yi} and Jacqueline Whang-Peng and Lin, {Hung Yun} and Kuan Wang",

year = "2025",

month = mar,

doi = "10.3892/or.2025.8865",

language = "English",

volume = "53",

journal = "Oncology Reports",

issn = "1021-335X",

publisher = "Spandidos Publications",

number = "3",

}

TY - JOUR

T1 - Heteronemin suppresses EGF‑induced proliferation through the PI3K/PD‑L1 signaling pathways in cholangiocarcinoma

AU - Yang, Yu Chen S.H.

AU - Tsai, Chung Che

AU - Yang, Yung Ning

AU - Liu, Feng Cheng

AU - Lee, Sheng Yang

AU - Yang, Jen Chang

AU - Crawford, Dana R.

AU - Chiu, Hsien Chung

AU - Lu, Mei Chin

AU - Li, Zi Lin

AU - Chen, Yi Chen

AU - Chu, Tin Yi

AU - Whang-Peng, Jacqueline

AU - Lin, Hung Yun

AU - Wang, Kuan

PY - 2025/3

Y1 - 2025/3

N2 - 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 antago‑ nist, 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.

AB - 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 antago‑ nist, 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.

KW - EGF

KW - PD‑L1

KW - cancer immunotherapy

KW - cholangiocarcinoma

KW - heteronemin

UR - http://www.scopus.com/inward/record.url?scp=85214899881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85214899881&partnerID=8YFLogxK

U2 - 10.3892/or.2025.8865

DO - 10.3892/or.2025.8865

M3 - Article

C2 - 39791224

AN - SCOPUS:85214899881

SN - 1021-335X

VL - 53

JO - Oncology Reports

JF - Oncology Reports

IS - 3

M1 - 32

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this