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Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

YUE ZHANG1,#, WENYU YANG1,#, XIAOWANG HAN1,#, YUE QIAO1, HAITAO WANG2, TING CHEN1, TIANYING LI1, WEN-BIN OU1,*

1 Department of Biopharmaceutics, College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
2 Department of Thoracic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, China

* Corresponding Author: WEN-BIN OU. Email: email

(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research 2024, 32(6), 1119-1128. https://doi.org/10.32604/or.2024.045025

Abstract

It has been shown that the high expression of human epididymis protein 4 (HE4) in most lung cancers is related to the poor prognosis of patients, but the mechanism of pathological transformation of HE4 in lung cancer is still unclear. The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma (LUAD). Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies, and through analysis of The Cancer Genome Atlas (TCGA) dataset. Frequent HE4 overexpression was demonstrated in LUAD, but not in lung squamous cell carcinoma (LUSC), indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC. HE4 knockdown significantly inhibited cell growth, colony formation, wound healing, and invasion, and blocked the G-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways. The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells, while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects. Moreover, we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD. Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

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APA Style
ZHANG, Y., YANG, W., HAN, X., QIAO, Y., WANG, H. et al. (2024). Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling. Oncology Research, 32(6), 1119-1128. https://doi.org/10.32604/or.2024.045025
Vancouver Style
ZHANG Y, YANG W, HAN X, QIAO Y, WANG H, CHEN T, et al. Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling. Oncol Res. 2024;32(6):1119-1128 https://doi.org/10.32604/or.2024.045025
IEEE Style
Y. ZHANG et al., "Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling," Oncol. Res., vol. 32, no. 6, pp. 1119-1128. 2024. https://doi.org/10.32604/or.2024.045025



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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