@article{16ab278fd0bc4242b253ec2e0aa27414,
title = "YAP Dictates Mitochondrial Redox Homeostasis to Facilitate Obesity-Associated Breast Cancer Progression",
abstract = "Dysregulation of hormones is considered a risk factor for obesity-mediated breast tumorigenesis; however, obesity is associated with poor outcomes among women diagnosed with triple-negative breast cancer (TNBC), which is a hormone-independent breast cancer subtype. Thus, identifying the driving force behind the obesity-breast cancer relationship is an urgent need. Here it is identified that diet-induced obesity (DIO) facilitates tumorigenesis of TNBC cells. Mechanistically, DIO induces a metabolic addiction to fatty acid oxidation (FAO), accompanied by coordinated activation of Yes-associated protein (YAP) signaling. Specifically, YAP governs mitochondrial redox homeostasis via transcriptional regulation of antioxidant-related enzymes, which renders tumor cells capable of extenuating FAO-elicited mitochondrial oxidative stress. Moreover, adipocytes-derived fatty acids are identified to be responsible for enhancing the FAO-YAP axis and antioxidative capacity, and higher expression of an obesity signature in breast cancer patients is positively correlated with YAP signaling and antioxidant genes. The findings uncover the crucial role of YAP in dictating mitochondrial redox homeostasis for obesity-mediated metabolic adaptation and breast tumor progression.",
keywords = "breast cancer, fatty acid oxidation, obesity, oxidative phosphorylation, YAP",
author = "Dai, {Jia Zih} and Wang, {Yen Ju} and Chen, {Cheng Hsun} and Tsai, {I. Lin} and Chao, {Yi Chun} and Lin, {Cheng Wei}",
note = "Funding Information: The authors thank the National RNAi Core Facility at Academia Sinica in Taiwan for providing shRNA reagents and relative services. The authors acknowledge the Laboratory Animal Center at Taipei Medical University (TMU) for technical support in animal experiments, the TMU Core Facility for technical support in the lipidomics analysis, and TMU. The authors acknowledge the academic and science graphic illustration service provided by the TMU Office of Research and Development. This study was supported by grants from the Ministry of Science and Technology, Taiwan (MOST106-2320-B-038-040, MOST107-2320-B-038-052-MY3, and MOST110-2320-B-038-021) and Chi Mei Medical Center (109CM-TMU-03 and 110CM-TMU-01). Funding Information: The authors thank the National RNAi Core Facility at Academia Sinica in Taiwan for providing shRNA reagents and relative services. The authors acknowledge the Laboratory Animal Center at Taipei Medical University (TMU) for technical support in animal experiments, the TMU Core Facility for technical support in the lipidomics analysis, and TMU. The authors acknowledge the academic and science graphic illustration service provided by the TMU Office of Research and Development. This study was supported by grants from the Ministry of Science and Technology, Taiwan (MOST106‐2320‐B‐038‐040, MOST107‐2320‐B‐038‐052‐MY3, and MOST110‐2320‐B‐038‐021) and Chi Mei Medical Center (109CM‐TMU‐03 and 110CM‐TMU‐01). Publisher Copyright: {\textcopyright} 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.",
year = "2022",
month = feb,
doi = "10.1002/advs.202103687",
language = "English",
volume = "9",
pages = "e2103687",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "12",
}