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Updated: Jan 26, 2026

Ovarian Cancer Patient-Derived Organoid Models for Pre-Clinical Drug Testing
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Ovarian Cancer Patient-Derived Organoid Models for Pre-Clinical Drug Testing

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DIRAS3-Derived Peptide Inhibits Autophagy in Ovarian Cancer Cells by Binding to Beclin1

Margie N Sutton1, Gilbert Y Huang2, Xiaowen Liang3

  • 1Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. MNSutton@mdanderson.org.

Cancers
|April 21, 2019
PubMed

Insights

Autophagy aids ovarian cancer cell survival and chemotherapy resistance. Researchers identified a peptide targeting DIRAS3 and Beclin1 to inhibit this autophagy, offering a potential new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Autophagy promotes cancer cell survival during starvation and enhances chemotherapy resistance.
  • Autophagy is critical for dormant, drug-resistant ovarian cancer cell survival.
  • DIRAS3, a tumor suppressor, inhibits cancer cell proliferation and motility, and its re-expression induces dormancy and autophagy.

Purpose of the Study:

  • To investigate the role of DIRAS3 in regulating autophagy in ovarian cancer.
  • To identify therapeutic strategies targeting DIRAS3-mediated autophagy.

Main Methods:

  • Utilized human xenograft models of ovarian cancer.
  • Analyzed clinical samples from "second look" operations.
  • Investigated the interaction between DIRAS3 and Beclin1.
  • Developed and tested an autophagy-inhibiting peptide based on DIRAS3.

Main Results:

  • DIRAS3 binds to Beclin1, forming the Autophagy Initiation Complex and triggering autophagosome formation.
  • An autophagy-inhibiting peptide derived from DIRAS3's switch II region, linked to Tat peptide, was successfully synthesized.
  • This peptide is taken up by ovarian cancer cells, binds Beclin1, and inhibits starvation-induced autophagy mediated by DIRAS3.

Conclusions:

  • DIRAS3 plays a key role in initiating autophagy in ovarian cancer cells.
  • A novel peptide targeting the DIRAS3-Beclin1 interaction effectively inhibits autophagy.
  • This peptide represents a promising therapeutic candidate for overcoming autophagy-driven chemoresistance in ovarian cancer.
Keywords:
ARHIBeclin1DIRAS3autophagy inhibitorovarian cancerpeptide therapeutic

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