Abstract: Disclosed is the discovery that the mTORC2 complex plays a role in the regulation of PKN3 phosphorylation at the turn motif threonine; and the use of the phosphorylation status of the turn motif threonine of PKN3 as a biomarker. In some embodiments, the phosphorylation status of the turn motif threonine of PKN3 is determined using an antibody that specifically binds to the turn motif threonine of a PKN3 protein, such as an anti-phosphoT860 antibody. In some embodiments, the invention relates to methods for screening compounds that have cancer therapeutic potential, methods for diagnosing cancer, methods for determining the prognosis of a patient suffering from cancer, methods for stratifying patients in a clinical trial, methods for treating a patient suffering from cancer, and methods for determining the effectiveness of a particular treatment regimen.

Abstract: Disclosed are compositions comprising and methods of using a novel macromolecular assembly comprising PKN3, PDK1 and RhoC (PPRC complex). The PPRC complex was shown to have kinase activity and was found in cells of high malignancy potential, such as particularly aggressive cancers. In some aspects, the invention provides methods for screening compounds that have cancer therapeutic potential, methods for diagnosing aggressive cancer, methods for determining the prognosis of a patient suffering from cancer, methods for stratifying patients in a clinical trial or determining the effectiveness of a particular treatment regimen, polypeptides that modulate the formation of the PPRC complex, and kits comprising one or more components of the PPRC complex.