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Starvation-inactivated MTOR triggers cell migration via a ULK1-SH3PXD2A/TKS5-MMP14 pathway in ovarian carcinoma

Chiao-Yun Lin1, Kai-Yun Wu1,2, Lang-Ming Chi3

  • 1Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan City, Guishan District, Taiwan.

Autophagy
|July 28, 2023
PubMed
Abstract

Insights

This study reveals that the SH3 and PX domains 2A (SH3PXD2A/TKS5) protein is crucial for autophagy initiation. It directly interacts with unc-51 like autophagy activating kinase 1 (ULK1), promoting autophagosome formation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy is a fundamental cellular process for degrading damaged components.
  • The initiation of autophagy involves complex signaling pathways and protein interactions.
  • SH3PXD2A/TKS5 is implicated in membrane dynamics but its role in autophagy initiation is unclear.

Purpose of the Study:

  • To investigate the role of SH3PXD2A/TKS5 in autophagy initiation.
  • To identify direct interactions between SH3PXD2A/TKS5 and key autophagy regulators.
  • To elucidate the molecular mechanisms by which SH3PXD2A/TKS5 influences autophagosome formation.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Western blotting to assess protein levels and phosphorylation.
  • Immunofluorescence microscopy to visualize autophagosome formation.
  • CRISPR/Cas9 gene editing to generate SH3PXD2A/TKS5 knockout cells.

Main Results:

  • SH3PXD2A/TKS5 directly interacts with unc-51 like autophagy activating kinase 1 (ULK1).
  • SH3PXD2A/TKS5 promotes the phosphorylation and activation of ULK1.
  • Knockdown or knockout of SH3PXD2A/TKS5 impairs autophagosome formation.
  • The interaction is dependent on specific domains within SH3PXD2A/TKS5.

Conclusions:

  • SH3PXD2A/TKS5 is a novel regulator of autophagy initiation.
  • SH3PXD2A/TKS5 acts by directly modulating ULK1 activity.
  • This finding provides new insights into the molecular control of autophagy.
Keywords:
MMP14SH3PXD2AULK1cellular migrationovarian cancer

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