YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas
Abstract Background 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 aden...
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doaj-3749494fb473419182b66ec9a3d01ece2021-01-10T12:31:26ZengBMCCancer Cell International1475-28672021-01-0121111310.1186/s12935-020-01688-9YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomasWei Xu0Mingjiong Zhang1Yue Li2Yu Wang3Kai Wang4Qiaoyu Chen5Runjie Zhang6Weiwei Song7Qiqing Huang8Weihong Zhao9Jianqing Wu10Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityCenter for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of MedicineJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background 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). Methods 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. Results 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. Conclusions Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.https://doi.org/10.1186/s12935-020-01688-9LUADsYAPPTEN/AKT/mTORAutophagy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Xu Mingjiong Zhang Yue Li Yu Wang Kai Wang Qiaoyu Chen Runjie Zhang Weiwei Song Qiqing Huang Weihong Zhao Jianqing Wu |
spellingShingle |
Wei Xu Mingjiong Zhang Yue Li Yu Wang Kai Wang Qiaoyu Chen Runjie Zhang Weiwei Song Qiqing Huang Weihong Zhao Jianqing Wu YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas Cancer Cell International LUADs YAP PTEN/AKT/mTOR Autophagy |
author_facet |
Wei Xu Mingjiong Zhang Yue Li Yu Wang Kai Wang Qiaoyu Chen Runjie Zhang Weiwei Song Qiqing Huang Weihong Zhao Jianqing Wu |
author_sort |
Wei Xu |
title |
YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas |
title_short |
YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas |
title_full |
YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas |
title_fullStr |
YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas |
title_full_unstemmed |
YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas |
title_sort |
yap manipulates proliferation via pten/akt/mtor-mediated autophagy in lung adenocarcinomas |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2021-01-01 |
description |
Abstract Background 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). Methods 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. Results 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. Conclusions Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling. |
topic |
LUADs YAP PTEN/AKT/mTOR Autophagy |
url |
https://doi.org/10.1186/s12935-020-01688-9 |
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