Metformin inhibits SUV39H1-mediated migration of prostate cancer cells.

ABSTRACT: Prostate cancer (PCa) is a leading cause of cancer-related death among men, largely due to incurable distant metastases. Metformin, the most common used anti-type-2 diabetes medicine, has been linked to reduced cancer risk and better diagnosis. We found that metformin was able to inhibit PCa cell migration, which correlates with tumor metastatic capability. The pathogenesis and progression of tumors are closely related to dysregulated gene expression in tumor cells through epigenetic alterations such as DNA methylation and histone modifications. We found that the level of SUV39H1, a histone methyltransferase of H3 Lys9, was reduced in metformin-treated PCa cells in a time-dependent manner. SUV39H1 overexpression increased PCa migration, whereas SUV39H1 depletion suppressed PCa cell migration. There is a positive correlation between SUV39H1 expression and PCa pathological stages. We further showed that both metformin treatment and SUV39H1 knockout in PCa cells can reduce integrin ?V and ?1 proteins, as well as their downstream phosphorylated focal adhesion kinase (FAK) levels, which is essential for functional adhesion signaling and tumor cell migration. Taken together, metformin reduced SUV39H1 to inhibit migration of PCa cells via disturbing the integrin-FAK signaling. Our study suggests SUV39H1 as a novel target to inhibit PCa cell migration.

SUBMITTER: Yu T 

PROVIDER: S-EPMC5523061 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature