YAP/TEAD-activated TAG synthesis and peroxidation in lipid droplets confer ROS resistance in cancer stem cells
Year: 2025
Type: article
Abstract: BACKGROUND: Cancer stem cells (CSCs) exhibit reduced levels of reactive oxygen species (ROS) despite increased oxidative phosphorylation, through mechanisms that remain poorly understood. Understanding these mechanisms could lead to new strategies for identifying and eradicating CSCs. METHODS: We combined lipidomic profiling, RNA-sequencing (RNA-seq), and TAGsig analysis to identify key lipids and genes involved in CSC-mediated resistance to ROS. These findings were further validated through a series of in vitro and in vivo experiments. RESULTS: YAP/TEAD pathway to activate transcription of TAG synthesis genes, enhancing resistance to ROS. CONCLUSION: We demonstrate that TAG in peri-mitochondrial LDs functions as a ROS scavenger, enabling CSCs to survive in hyperoxidative environments. Targeting the signaling pathways involved in TAG synthesis presents a potential strategy for eradicating CSCs.
Source: Redox Biology
Authors: Jiun-Han Lin, Tien-Wei Hsu, Wei-Chung Cheng, Chen-Chi Liu, Anna Fen-Yau Li, Mien-Chie Hung, Han-Shui Hsu, Shih-Chieh Hung
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,310
Awards: G1844839517, Molecular Mechanisms of Lung Cancer Stem Cell Resistance to Oxidative Phosphorylation and Ferroptosis, G5483878852, Nanomedicine Using Collagen Xii-Targeting Peptide for Osteoarthritis Theranostics and Regenerative Medicine( I ), Lipid Profile and Its Association with Reactive Oxygen Species Levels and Radioresistance in Cancer Stem Cells., Investigation of the Origin and the Roles of Cancer-Associated Fibroblasts in Colorectal Cancer Progression and Immune Evasion, Nanomedicine Using Collagen Xii-Targeting Peptide for Osteoarthritis Theranostics and Regenerative Medicine( II ), The Mechanisms of Hsp27 in Regulation of Ferroptosis in Esophageal Cancer Stem Cells
OpenAlex ID: W4417138581