Common corruption of the mTOR signaling network in human tumors.
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.
Menon
S
S
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Manning
B D
BD
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D047908:Intracellular Signaling Peptides and Proteins; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus