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Updated: Jun 2, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

861

A targetable OSGIN1 - AMPK - SLC2A3 axis controls the vulnerability of ovarian cancer to ferroptosis

Mengqi Deng1,2, Fan Tang1,2, Xiangyu Chang1,2

  • 1Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, 100006, Beijing, China.

NPJ Precision Oncology
|January 14, 2025
PubMed

Insights

Loss of OSGIN1 promotes ovarian cancer growth and drug resistance by upregulating SLC2A3, hindering ferroptosis. Targeting SLC2A3 with antibodies enhances chemotherapy, offering a new ovarian cancer treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Stress Response

Background:

  • Ovarian cancer treatment options remain limited despite chemotherapy advances.
  • Oxidative stress-induced growth inhibitor 1 (OSGIN1) is a tumor suppressor gene implicated in ovarian cancer.
  • The role of OSGIN1 in ferroptosis regulation within ovarian cancer is not well understood.

Purpose of the Study:

  • To investigate the role and regulatory mechanism of OSGIN1 in ovarian cancer cells.
  • To elucidate how OSGIN1 influences ferroptosis in ovarian cancer.

Main Methods:

  • Investigated OSGIN1 gene function in ovarian cancer cells.
  • Analyzed the activation of AMPK signaling pathway via ATM.
  • Examined the expression of SLC2A3.
  • Utilized SLC2A3-neutralizing antibody in patient-derived xenograft models.

Main Results:

  • Loss of OSGIN1 accelerated ovarian cancer growth and induced resistance to ferroptosis.
  • OSGIN1 deficiency activated ATM/AMPK signaling, upregulating SLC2A3.
  • Upregulated SLC2A3 protected ovarian cancer cells from ferroptosis.
  • An SLC2A3-neutralizing antibody potentiated sorafenib's ferroptosis-inducing and anti-cancer effects in vivo.

Conclusions:

  • OSGIN1 loss promotes ovarian cancer progression and ferroptosis resistance through the ATM/AMPK/SLC2A3 pathway.
  • Targeting SLC2A3 represents a promising therapeutic strategy to enhance ferroptosis-based ovarian cancer treatment.

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