Scholarlink

<p>Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Oxidative stress-induced growth inhibitor 1 (<i>OSGIN1)</i>, which is a tumor suppressor gene known to regulate the cellular stress response and apoptosis, is associated with ovarian cancer development. However, the underlying mechanisms involved in ferroptosis regulation have not been elucidated. Thus, this study aimed to investigate the effect and underlying regulatory mechanism of the <i>OSGIN1</i> gene on ovarian cancer cells. Our results demonstrated that loss of the <i>OSGIN1</i> gene promoted ovarian cancer growth and conferred resistance to drug-induced ferroptosis. Mechanistically, the loss of OSGIN1 activates AMPK signaling through ATM, leading to the upregulation of SLC2A3, which protects cells from ferroptosis and renders them insensitive to ferroptosis inducers. Notably, an SLC2A3-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on ovarian cancer patient-derived xenograft tumors. Overall, anti-SLC2A3 therapy is a promising method to improve ovarian cancer treatment by targeting ferroptosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月14日

查看全文
  • Mengqi Deng,
  • Fan Tang,
  • Xiangyu Chang,
  • Yanqin Zhang,
  • Penglin Liu,
  • Xuechao Ji,
  • Yubo Zhang,
  • Ruiye Yang,
  • Junyi Jiang,
  • Junqi He,
  • Jinwei Miao

摘要

Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Oxidative stress-induced growth inhibitor 1 (OSGIN1), which is a tumor suppressor gene known to regulate the cellular stress response and apoptosis, is associated with ovarian cancer development. However, the underlying mechanisms involved in ferroptosis regulation have not been elucidated. Thus, this study aimed to investigate the effect and underlying regulatory mechanism of the OSGIN1 gene on ovarian cancer cells. Our results demonstrated that loss of the OSGIN1 gene promoted ovarian cancer growth and conferred resistance to drug-induced ferroptosis. Mechanistically, the loss of OSGIN1 activates AMPK signaling through ATM, leading to the upregulation of SLC2A3, which protects cells from ferroptosis and renders them insensitive to ferroptosis inducers. Notably, an SLC2A3-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on ovarian cancer patient-derived xenograft tumors. Overall, anti-SLC2A3 therapy is a promising method to improve ovarian cancer treatment by targeting ferroptosis.