YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas
Wei Xu1, Mingjiong Zhang1, Yue Li1,2
1Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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.
Insights
The transcriptional coactivator YAP promotes lung adenocarcinoma proliferation by regulating autophagy through the PTEN/AKT/mTOR pathway. YAP overexpression correlates with reduced survival in lung adenocarcinoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Autophagy plays a complex role in tumor development.
- The Hippo pathway's YAP protein is implicated in autophagy.
- Lung adenocarcinomas (LUAD) present a significant clinical challenge.
Purpose of the Study:
- To investigate the role of YAP in regulating LUAD cell proliferation via autophagy.
- To elucidate the molecular mechanisms linking YAP, autophagy, and LUAD progression.
Main Methods:
- Analysis of LUAD patient data (GSE43458).
- Assessment of YAP expression using RT-qPCR and Western blot.
- Evaluation of YAP's effect on LUAD cell proliferation and autophagy in vitro and in vivo using CCK-8 assays, xenograft models, and GFP-mRFP-LC3 fusion proteins.
Main Results:
- YAP is overexpressed in LUAD and linked to poorer 5-year survival.
- YAP influences proliferation and autophagy in LUAD cell lines (A549, H1299).
- YAP activates Akt/mTOR signaling by suppressing PTEN in a Hippo-dependent manner, promoting proliferation.
Conclusions:
- YAP, a key Hippo pathway coactivator, drives lung adenocarcinoma proliferation.
- This proliferation is modulated by PTEN/AKT/mTOR-mediated autophagic signaling.
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