通过FDX1驱动的自噬调节卵巢癌进展。

Modulating ovarian cancer progression through FDX1-driven autophagy.

作者信息

Liu Chang, Wang Siyu, Zhao Jiabao, Qiu Hui, Du Hongmei

机构信息

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Obstetric and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

NPJ Precis Oncol. 2025 Jul 8;9(1):230. doi: 10.1038/s41698-025-00994-7.

DOI:10.1038/s41698-025-00994-7

PMID:40629130

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12238385/

Abstract

Ferredoxin 1 (FDX1) emerges as a crucial regulator of autophagy and copper metabolism in ovarian cancer (OC), as revealed by this investigation. Predominantly localized to the cytoplasm and mitochondria, FDX1 coordinates autophagic activity by modulating the AMPK and mTOR signaling pathways. Its role extends to preserving mitochondrial integrity and facilitating sulfation of DLAT/DLST, ensuring effective autophagic flux. Knockdown of FDX1 disrupts these processes, exacerbating mitochondrial dysfunction. In vivo studies further demonstrate that overexpressing FDX1, combined with Compound C treatment, markedly inhibits tumor growth and Ki67 expression. These results position FDX1 as a promising target for therapeutic strategies aimed at exploiting autophagy to hinder OC progression.

摘要

本研究表明，铁氧化还原蛋白1（FDX1）是卵巢癌（OC）自噬和铜代谢的关键调节因子。FDX1主要定位于细胞质和线粒体，通过调节AMPK和mTOR信号通路来协调自噬活性。其作用还包括维持线粒体完整性以及促进DLAT/DLST的硫酸化，确保有效的自噬通量。敲低FDX1会破坏这些过程，加剧线粒体功能障碍。体内研究进一步表明，过表达FDX1并联合Compound C治疗可显著抑制肿瘤生长和Ki67表达。这些结果表明，FDX1是一种有前景的治疗靶点，有望通过利用自噬来阻碍OC进展。