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Updated: Aug 14, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPK/YAP

Yuan-Li Wang1, Qi Wang1, Hua Li1

  • 1Department of Respiratory Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.

Neoplasma
|January 9, 2023
PubMed

Insights

Sestrin2 inhibits non-small cell lung cancer (NSCLC) growth and metastasis by targeting the AMPK/YAP/FOXM1 pathway. This discovery offers a new therapeutic strategy for NSCLC, a disease with high mortality rates.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Non-small cell lung cancer (NSCLC) presents high incidence and mortality, with poor prognosis due to uncontrolled cell growth and metastasis.
  • Understanding the molecular mechanisms underlying NSCLC progression is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of Sestrin2 in the epithelial-mesenchymal transition (EMT) process of NSCLC cells.
  • To elucidate the underlying molecular mechanisms, focusing on the Sestrin2-AMPK/YAP/FOXM1 axis.

Main Methods:

  • Utilized NSCLC cell lines and nude mice models.
  • Employed qRT-PCR, western blot, CCK-8, EdU assay, scratch test, Transwell assay, bioinformatics analysis, and Co-IP assay.
  • Investigated gene and protein expression, cell proliferation, migration, invasion, and molecular interactions.

Main Results:

  • Sestrin2 expression was decreased, while YAP expression was elevated in NSCLC cells.
  • Sestrin2 sufficiency or YAP silencing inhibited NSCLC cell growth and metastasis.
  • YAP interacted with TEAD to enhance FOXM1 expression, which counteracted Sestrin2's inhibitory effects.
  • Sestrin2 attenuated tumor growth in mice by modulating the AMPK/YAP/FOXM1 axis.

Conclusions:

  • Sestrin2 inhibits NSCLC cell proliferation, migration, invasion, and EMT.
  • Sestrin2 acts by suppressing YAP activation via AMPK phosphorylation and subsequently reducing FOXM1 expression through YAP/TEAD interplay.
  • This study reveals a novel mechanism for Sestrin2 in NSCLC, suggesting its potential as a therapeutic target.

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