Aberrant regulation of serine metabolite drives extracellular vesicle release and cancer progression

Abstract

AbstractCancer cells secrete extracellular vesicles (EVs) to regulate cells in the tumor microenvironment for their own benefit to grow and survive in the patient’s body. Although emerging evidence has demonstrated the molecular mechanisms of EV release, regulating cancer-specific EV secretion remains challenging. In this study, we applied a microRNA (miRNA) library to reveal the universal mechanisms of EV secretion in cancer cells. Here, we identified miR-891b and its direct target gene, phospho-aminotransferase 1 (PSAT1), which promotes EV secretion through the serine synthesis pathway. Inhibition of PSAT1 affected EV secretion in multiple types of cancer, suggesting that the miR-891b/PSAT1 axis shares a common mechanism of cancer EV secretion. Interestingly, PSAT1 also controlled cancer metastasis via EV secretion. Our data provide insights into the PSAT1-controlled EV secretion mechanism and its potential as a therapeutic target in multi types of cancer.