TRPML1 triggers ferroptosis defense and is a potential therapeutic target in AKT-hyperactivated cancer

Authors: Hai-Liang Zhang, Bing-Xin Hu, Zhi-Peng Ye, Zhi-Ling Li, Shan Liu, Wen-Qing Zhong, Tian Du, Dong Yang, Jia Mai, Li-Chao Li, Yu-Hong Chen, Xian-Ying Zhu, Xuan Li, Gong-Kan Feng, Xiao-Feng Zhu, Rong Deng

Published: 2024-06-26

DOI: 10.1126/scitranslmed.adk0330

Source: Full article


Abstract

Targeting ferroptosis for cancer therapy has slowed because of an incomplete understanding of ferroptosis mechanisms under specific pathological contexts such as tumorigenesis and cancer treatment. Here, we identify TRPML1-mediated lysosomal exocytosis as a potential anti-ferroptotic process through genome-wide CRISPR-Cas9 activation and kinase inhibitor library screening. AKT directly phosphorylated TRPML1 at Ser