In this study, we reported the effect of the ATP binding site competitive inhibitor Torin1 on activatedα2-macroglobulin (α2M*)-induced cell proliferation and activation of mTORC1 and mTORC2 signaling in prostate cancer cells. Torin1 significantly inhibitedα2M*-induced cellproliferation as measured by protein and DNA synthesis. Translational activity, a major cellular response in malignant cells,is coordinately regulated by the mTORC1-S6-kinaseand mTORC1-4EBP1 axes. Torin1 significantly inhibitedα2M*- and insulin-induced activation of mTORC1 as determined by phosphorylation of S6-kinaseat Thr389and 4EBP1 at Thr37/46 compared to untreated cells employing Raptor immunoprecipitates. Torin1 also significantly inhibitedα2M*- and insulin-induced upregulation of p-AktT308 and p-AktS473 inprostate cancer cells. The effect was comparable to that of insulin employed as a positive control. Finally, Torin1 inhibitedα2M*- and insulin-induced activation of mTORC2 kinase assayas measured by phosphorylation of Akt at Ser473inRictor immunoprecipitates of prostate cancer cells.
Cite this paper
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