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

作　　者：YUE ZHANG WENYU YANG XIAOWANG HAN YUE QIAO HAITAO WANG TING CHEN TIANYING LI WEN-BIN OU 

机构地区：[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

出　　处：《Oncology Research》2024年第6期1119-1128,共10页肿瘤学研究（英文）

基　　金：supported by National Natural Science Foundation of China(82272695);the Key Program of Natural Science Foundation of Zhejiang Province(LZ23H160004);National Undergraduate Training Program for Innovation,and Zhejiang Xinmiao Talents Program,China.

摘　　要：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 G1-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.

关 键 词：Lung adenocarcinoma Human epididymis protein 4 Epidermal growth factor receptor BIOMARKER Targeted therapies 

分 类 号：R734.2[医药卫生—肿瘤]