Chronic stress-induced cholesterol metabolism abnormalities promote ESCC tumorigenesis and predict neoadjuvant therapy response.

ABSTRACT: Recent studies have demonstrated that chronic stress can enhance the development of multiple human diseases, including cancer. However, the role of chronic stress in esophageal carcinogenesis and its underlying molecular mechanisms remain unclear. This study uncovered that dysregulated cholesterol metabolism significantly promotes esophageal carcinogenesis under chronic stress conditions. Our findings indicate that the persistent elevation of glucocorticoids induced by chronic stress stimulates cholesterol uptake, contributing to esophageal carcinogenesis. The activated glucocorticoid receptor (GCR) enrichment at the promoter region of High Mobility Group Box 2 (HMGB2) facilitates its transcription. As a transcription coactivator, HMGB2 enhances Sterol Regulatory Element Binding Transcript

SUBMITTER: Wang T 

PROVIDER: S-EPMC11804521 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature