Sestrin2 Overexpression Inhibits Proliferation and Epithelial-Mesenchymal Transition and Induces Autophagy Through the AMPK/mTOR Signaling Pathway in Human Prostate Cancer Cells.

Prostate cancer is the most common malignancy in men. Sestrin2 (SESN2) has antitumor activity against several types of cancers. However, the effect of SESN2 on prostate cancer is not well known. In this study, we showed that SESN2 inhibits human prostate cancer. To investigate the contribution of Sestrin2 to prostate cancer, we performed a bioinformatic analysis of the Cancer Genome Atlas database and Gene Expression Profiling Interactive Analysis. Using the Sestrin2 overexpression vector, we identified proliferation, migration, and invasion in prostate cancer cells. Furthermore, the effect of Sestrin2 on autophagy was confirmed by Western blot analysis and immunofluorescence staining. We showed that expression of SESN2 was reduced in prostate cancer tissues and cell lines, and low expression of SESN2 correlated with decreased survival in prostate cancer patients. We have shown that SESN2 inhibits cell viability and cell proliferation-related protein levels in PC3 and DU145 prostate cancer cells. SESN2 inhibited EMT-related protein and migration and invasion levels. SESN2 promoted autophagy by increasing autophagy-related protein levels and LC3-positive cells. SESN2 increased pAMPK and decreased pmTOR protein levels. Furthermore, we used rapamycin, an mTOR inhibitor, to determine whether the AMPK/mTOR signaling pathway regulates autophagy in prostate cancer cells. Our study suggests that SESN2 inhibits prostate cancer cells by inducing autophagy through the AMPK/mTOR signaling pathway. These results indicate that SESN2 might be a novel target for prostate cancer.