Expression modulation of different S6Ks isoforms in prostate cancer cell lines leads to alterations in proliferation, migration and chemotherapy resistance

Abstract

The mTOR pathway is stimulated by high amounts of amino acids, ATP, and insulin and several studies have shown that mTOR is active in various biochemical processes involved in cell growth and metabolism. The S6Ks proteins have shown an important role in the mTOR signaling, acting as effectors of this pathway. Many works have demonstrated the participation of the mTOR pathway in cancer, but there is currently a demand to better characterize the S6Ks isoforms in this disease. The present work aimed to study the roles of p70‐S6K1, p85‐S6K1 and p54‐S6K2 isoforms in cancer, using DU145 and PC3 prostate cancer cell lines. Our results indicate that p85‐S6K1 isoform enhances proliferation and colony formation of DU145 and PC3 cells. Besides, overexpression of both S6K1 isoforms increased migration of PC3 cells in scratch assay. Moreover, all S6Ks isoforms when overexpressed increased docetaxel resistance of PC3 cells. Finally, knockdown experiments against S6K1 and S6K2 had complemented our data so far. In conclusion, we have identified different cellular effects of S6Ks isoforms in an in vitro model of prostate cancer