FAT4 activation inhibits epithelial-mesenchymal transition (EMT) by promoting autophagy in H2228/Cer cells

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Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

979

Yuying Yang1, Yang Li1, Qian Yang1

  • 1Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 103 Wenhua Road, Shenyang, 110016, China.

Medical Oncology (Northwood, London, England)
|December 28, 2022
PubMed

Insights

FAT4 activation inhibits epithelial-mesenchymal transition (EMT) in ceritinib-resistant lung cancer by promoting autophagy. This finding offers a new therapeutic target for anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • FAT atypical cadherin 4 (FAT4) acts as a tumor suppressor in lung cancer, influencing epithelial-mesenchymal transition (EMT).
  • The role of FAT4 in ceritinib-resistant anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) EMT remains unexplored.

Purpose of the Study:

  • To investigate the role of FAT4 in the EMT of ceritinib-resistant ALK-positive NSCLC.
  • To elucidate the potential mechanisms underlying FAT4's interaction in this process.

Main Methods:

  • Assessed FAT4 expression in ceritinib-resistant NCI-H2228 (H2228/Cer) cells.
  • Utilized Jujuboside A, a FAT4 activator, to evaluate its effects on EMT and metastasis.
  • Investigated the interplay between FAT4, autophagy, and EMT pathways.

Main Results:

  • FAT4 expression was significantly downregulated in H2228/Cer cells.
  • Jujuboside A treatment reduced EMT and metastasis in H2228/Cer cells.
  • Autophagy inhibition reversed the anti-EMT effects of FAT4 activation, implicating FAT4 in autophagy regulation via PSMD4 and PSMB4.

Conclusions:

  • FAT4 activation inhibits EMT in ceritinib-resistant ALK-positive NSCLC by promoting autophagy.
  • This mechanism involves pathways such as ROS/NF-κB/IκB-α and Wnt/β-catenin.
  • FAT4 represents a potential therapeutic target for overcoming ceritinib resistance in ALK-positive NSCLC.
Keywords:
AutophagyCeritinib resistanceEpithelial-mesenchymal transitionFAT atypical cadherin 4

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