Psychological Stress Associated Bile Acid Reprogramming Promotes Hepatocellular Carcinoma Progression
Source abstract
Abstract
ABSTRACT Psychological stress, particularly depression, is increasingly recognized as a non‐genetic determinant of cancer progression, yet its role in hepatocellular carcinoma (HCC) remains unclear. By integrating three prospective cohorts (CHARLS, NHANES, and UK Biobank; n = 492,501), we show that depression was associated with increased HCC risk (CHARLS: hazard ratio (HR) = 2.28, 95% confidence interval (CI) 1.06–4.93; NHANES: odds ratio (OR) = 5.95, 95% CI 2.42–14.0; UK Biobank: HR = 1.39, 95% CI 1.10–1.79). Using patient samples, multi‐omics analyses, and social isolation (SI) models, we identified taurocholate as a key metabolite elevated in psychological stress‐associated HCC. Taurocholate stabilizes CBX5 by weakening its interaction with E3 ubiquitin ligases. CBX5 cooperated with MYC to activate PHGDH transcription, thereby reducing ferroptotic sensitivity and promoting tumor growth. Importantly, ursodeoxycholic acid (UDCA), a clinically approved bile acid modulator, reduced taurocholate levels and suppressed tumor growth in SI‐associated HCC models. Together, these findings support a mechanistic link between depression and HCC progression via bile acid metabolic reprogramming and identify the taurocholate‐CBX5‐MYC‐PHGDH axis as a potential therapeutic target.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Ferroptosis and cancer prognosis · Drug Transport and Resistance Mechanisms · Epigenetics and DNA Methylation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Urology The Second Xiangya Hospital Central South University Changsha Hunan China
Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education National Clinical Research Center for Metabolic Disease Changsha China
Uro‐Oncology Institute of Central South University Changsha Hunan China
Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya Hospital Central South University Changsha Hunan China
Cancer Center, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Department of Cardiology The First Affiliated Hospital of University of South China Hengyang P. R. China
CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai China
Department of Hepatobiliary and Pancreas Surgery, Sichuan Provincial People's Hospital School of Medicine, University of Electronic Science and Technology of China Chengdu Sichuan China
Department of Cardiovascular Medicine The Second Xiangya Hospital of Central South University Changsha P. R. China
FuRong Laboratory Changsha Hunan China
Key Laboratory of Cardiometabolic Medicine in Hunan Province China
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