Panner Amith, Parsa Andrew T, Pieper Russell O
The Brain Tumor Research Center and the Department of Neurological Surgery, The University of California-San Francisco, San Francisco, California 94143-0875, USA.
Cell Cycle. 2006 Jan;5(2):147-50. doi: 10.4161/cc.5.2.2359. Epub 2006 Jan 16.
TNF-related apoptosis-inducing ligand (TRAIL) is a peptide that induces apoptosis to varying degrees in tumor cells. While TRAIL sensitivity in tumors has been linked to c-myc- and MEK/Erk-induced enhancement of caspase activation, our recent study identified a third input controlling TRAIL sensitivity, namely the Akt-mTOR pathway. We showed that instead of enhancing TRAIL sensitivity, Akt expression, acting through mTOR and the mTOR targets S6 kinase and eIF-4E, selectively enhances translation of the anti-apoptotic protein FLIP(S) and confers TRAIL resistance. In this perspective article we will discuss the linkage of the Akt-mTOR pathway to other regulators of TRAIL sensitivity, its importance in controlling a broader range of apoptotic events, its utility in predicting TRAIL responsiveness, and its potential manipulation for therapeutic benefit.
