U. K. Misra, S. Payne and S. V. Pizzo, “Ligation of Prostate Cancer Cell Surface GRP78 Activates a Pro-Proliferative and Anti-Apoptotic Feedback Loop: A Role for Secreted Prostate Specific Antigen,” The Journal of Biological Chemistry, Vol. 286, No. 2, 2011, pp. 1248-1259. doi:10.1074/jbc.M110.129767

has been cited by the following article:

• TITLE: iTorin1—An Active Site Inhibitor of mTOR, Suppresses Prostate Cancer Cell Growth Induced by Activated α2M-Macroglobulin Ligation of Cell Surface GRP78

  AUTHORS: Uma K. Misra, Salvatore V. Pizzo

  KEYWORDS: α2-Macroglobulin; Torin1; Prostate Cancer Cells Proliferation; p-S6KT389; p-4EBP1; p-AktS473; Insulin

  JOURNAL NAME: Journal of Cancer Therapy, Vol.4 No.4A, April 30, 2013

  ABSTRACT: In this study, we reported the effect of the ATP binding site competitive inhibitor Torin1 on activated α2-macroglobulin (α2M*)-induced cell proliferation and activation of mTORC1 and mTORC2 signaling in prostate cancer cells. Torin1 significantly inhibited α2M*-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 inhibited α2M*- and insulin-induced activation of mTORC1 as determined by phosphorylation of S6-kinaseat Thr389 and 4EBP1 at Thr37/46 compared to untreated cells employing Raptor immunoprecipitates. Torin1 also significantly inhibited α2M*- and insulin-induced upregulation of p-AktT308 and p-AktS473 in prostate cancer cells. The effect was comparable to that of insulin employed as a positive control. Finally, Torin1 inhibited α2M*- and insulin-induced activation of mTORC2 kinase assayas measured by phosphorylation of Akt at Ser473 inRictor immunoprecipitates of prostate cancer cells.