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.

Abstract

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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