Common corruption of the mTOR signaling network in human tumors

Abstract

The mammalian target of rapamycin (mTOR) is responsive to numerous extracellular and intracellular cues and, through the formation of two physically and functionally distinct complexes, has a central role in the homeostatic control of cell growth, proliferation and survival. Through the aberrant activation of mTOR signaling, the perception of cellular growth signals becomes disconnected from the processes promoting cell growth, and this underlies the pathophysiology of a number of genetic tumor syndromes and cancers. Here, we review the oncogenes and tumor suppressors comprising the regulatory network upstream of mTOR, highlight the human cancers in which mTOR is activated and discuss how dysregulated mTOR signaling provides tumors a selective growth advantage. In addition, we discuss why activation of mTOR, as a consequence of distinct oncogenic events, results in diverse clinical outcomes, and how the complexity of the mTOR signaling network might dictate therapeutic approaches.

Figure 1. Oncogenes and tumor suppressors converge on the regulation of mTORC1

Model of the common oncogenic signaling pathways regulating mTORC1 activation. Proteins encoded by oncogenes are indicated with asterisks (**), and those encoded by tumor suppressor genes are depicted in red. See text for details.