A research team led by Professor Dong Zigang from Zhengzhou University (ZZU) has identified a key mechanism by which chronic stress drives the progression of esophageal squamous cell carcinoma (ESCC). The study, published in the journal Cancer Research, reveals a novel RNA modification-metabolic regulatory circuit and provides new potential therapeutic targets.
Chronic stress is a well-recognized risk factor for various diseases, including cancer. Through clinical sample analysis, the team found that ESCC patients with stress-related profiles had elevated serum adrenaline levels and enhanced pentose phosphate pathway activity. Mechanistically, chronic stress activates the ADRB2 signaling pathway, which stabilizes MYCBP protein and enhances MYC transcriptional activity, upregulating key enzymes in the pentose phosphate pathway. This drives metabolic reprogramming that promotes tumor progression.
The study also uncovered a positive feedback loop: chronic stress not only activates ADRB2 signaling but also enhances ADRB2 mRNA translation through RNMT-mediated m7G cap modification, further amplifying the pro-tumor effect.
This work establishes a clear link between stress-induced RNA modification and tumor metabolism, offering new insights for precision prevention and treatment of ESCC.
A schematic illustrating the mechanism by which the chronic stress-related m7G-ADRB2-PPP axis regulates the progression of esophageal squamous cell carcinoma. [Photo/zzu.edu.cn]