YAP Manipulates Proliferation Via PTEN/AKT/mTOR-mediated Autophagy in Lung Adenocarcinomas

Abstract

Background: Autophagy is a double-edged sword during the initiation or progression of multiple tumors. Hippo pathway core-factor YAP has been proved to be involved in autophagy processes. The present study aimed to identify the mechanism underlying modulation of YAP via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas (LUAD).Methods: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were used to assess YAP expression in LUAD cell lines. CCK-8 assay, flow cytometry, 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 and rescue experiments were carried out to elucidate the mechanism by which YAP manipulating autophagy in LUAD cells.Results: YAP significantly overexpressed in samples of LUAD patients and related to 5-year survival. YAP manipulates the proliferation and autophagy of A549 and H1299 LUAD cells. YAP induces 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.

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