Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein

Nan Lin1,2, Liankun Sun2, Jiannan Chai3

  • 1First Hospital of Jilin University, Changchun, China.

Cancer Cell International
|January 18, 2024
PubMed

Insights

Stress granules (SGs) contribute to drug resistance in ovarian cancer by intercepting ATF5 and regulating mitochondrial responses. Targeting SGs may offer new strategies against drug-resistant ovarian cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Stress Response

Background:

  • Drug resistance is a major obstacle in ovarian cancer treatment.
  • The adaptive stress response, particularly stress granules (SGs), is increasingly recognized as a key mechanism in cancer drug resistance.

Purpose of the Study:

  • To investigate the role of stress granules (SGs) in mediating drug resistance in ovarian cancer cells.
  • To explore the interaction between SGs, signaling factors, and organelle responses under drug treatment.

Main Methods:

  • Utilized A2780 and SKOV3 ovarian cancer cell lines.
  • Treated cells with the dual PI3K/mTOR inhibitor PKI-402.
  • Analyzed the formation of stress granules and their interaction with ATF5 and the mitochondrial unfolded protein response (UPRmt).

Main Results:

  • PKI-402 induced stress granule formation in A2780 ovarian cancer cells.
  • Stress granules were found to intercept the signaling factor ATF5.
  • Stress granule formation was linked to the regulation of the mitochondrial unfolded protein response (UPRmt).

Conclusions:

  • Stress granules play a significant role in the adaptive stress response contributing to drug resistance in ovarian cancer.
  • The interaction between stress granules and signaling pathways like ATF5, and organelle responses like UPRmt, is crucial for understanding drug resistance.
  • Investigating the network of SGs and membrane-bound organelles offers novel insights into antitumor drug mechanisms.

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