Abstract
BackgroundAKT signaling promotes cell growth, proliferation and survival and is hyperactivated in many cancers. TOR complex 2 (TORC2) activates AKT by phosphorylating it on the 'hydrophobic motif' site. Hydrophobic motif site phosphorylation is needed only for a subset of AKT functions. Whether proliferation of tumor cells depends on TORC2 activity has not been thoroughly explored.MethodsWe used RNAi-mediated knockdown of rictor to inhibit TORC2 activity in MCF7 and PC3 tumor cells to analyze the importance of TORC2 on proliferation of tumor cells.ResultsTORC2 inhibition reduced proliferation and anchorage-independent growth of both cell lines. Rictor depleted cells accumulated G1 phase, and showed prominent downregulation of Cyclin D1.ConclusionThis study provides further evidence that inhibition of TORC2 activity might be a useful strategy to inhibit proliferation of tumor cells and subsequent tumor growth.
Highlights
AKT signaling promotes cell growth, proliferation and survival and is hyperactivated in many cancers
Our results suggest that inhibition of TOR complex 2 (TORC2) activity might be a useful strategy to inhibit proliferation of tumor cells and subsequent tumor growth
Rictor depletion inhibits AKT phosphorylation and activity in MCF7 and PC3 tumor cells In order to analyze the importance of TOR complex 2 for growth of tumor cells, we sought to prevent its activity by downregulating Rictor, an essential component of TORC2 [9,10]
Summary
AKT signaling promotes cell growth, proliferation and survival and is hyperactivated in many cancers. TOR complex 2 (TORC2) activates AKT by phosphorylating it on the 'hydrophobic motif' site. Hydrophobic motif site phosphorylation is needed only for a subset of AKT functions. Whether proliferation of tumor cells depends on TORC2 activity has not been thoroughly explored. AKT signaling promotes cell growth, proliferation and survival and is hyperactivated in numerous cancers (Reviewed in [1,2]). AKT kinase activity is principally determined by the level of phosphatidylinositol-3,4,5-triphosphate (PIP3) in the plasma membrane of cells, which is generated by phosphatidylinositol-3-kinase (PI3K) upon stimulation of receptor tyrosine kinases. When PIP3 levels are elevated, AKT is recruited to the plasma membrane and phosphorylated in the activation loop by PDK1. TORC2-mediated phosphorylation only affects a subset of AKT functions. While Drosophila AKT and its upstream regulators, such as PI3K and (page number not for citation purposes)
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