Xu Wei, Zhang Mingjiong, Li Yue, Wang Yu, Wang Kai, Chen Qiaoyu, Zhang Runjie, Song Weiwei, Huang Qiqing, Zhao Weihong, Wu Jianqing
Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Zhongda Hospital Lishui Branch, Nanjing Lishui People's Hospital, Southeast University, Nanjing, China.
Cancer Cell Int. 2021 Jan 7;21(1):30. doi: 10.1186/s12935-020-01688-9.
Autophagy is a double-edged sword during the initiation and progression of multiple tumors. The Hippo pathway effector YAP has been proved to be involved in autophagy processes. The present study aimed to investigate how YAP regulates cell proliferation via autophagy in lung adenocarcinomas (LUAD).
Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were performed to assess YAP expression in LUAD cell lines. CCK-8 assay, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor treatment and rescue experiments were carried out to elucidate the mechanism by which YAP manipulates autophagy in LUAD cells.
YAP was significantly overexpressed in samples of LUAD patients and its expression level is related to 5-year survival. YAP manipulated the proliferation and autophagy in A549 and H1299 LUAD cells. YAP could induce activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo.
Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.
自噬在多种肿瘤的发生和发展过程中是一把双刃剑。Hippo信号通路效应分子YAP已被证明参与自噬过程。本研究旨在探讨YAP如何通过自噬调节肺腺癌（LUAD）细胞的增殖。
从基因表达综合数据库（GEO）获取LUAD芯片GSE43458的数据。采用RT-qPCR和蛋白质免疫印迹法评估YAP在LUAD细胞系中的表达。利用CCK-8检测、异种移植肿瘤模型、免疫组化和GFP-mRFP-LC3融合蛋白评估YAP对LUAD细胞体外和体内自噬的影响。进行自噬抑制剂处理和拯救实验，以阐明YAP调控LUAD细胞自噬的机制。
YAP在LUAD患者样本中显著高表达，其表达水平与5年生存率相关。YAP调控A549和H1299 LUAD细胞的增殖和自噬。YAP可通过以Hippo信号通路依赖的方式抑制PTEN来诱导Akt/mTOR信号通路的激活。3-甲基腺嘌呤阻碍自噬流并促进体外和体内的增殖。
Hippo信号通路关键转录共激活因子YAP调控肺腺癌的增殖，这一过程受PTEN/AKT/mTOR自噬信号通路调节。
