The Akt-mTOR tango and its relevance to cancer.
The downstream effector of PI3K, Akt, is frequently hyperactivated in human cancers. A critical downstream effector of Akt, which contributes to tumorigenesis, is mTOR. In the PI3K/Akt/mTOR pathway, Akt is flanked by two tumor suppressors: PTEN, acting as a brake upstream of Akt, and TSC1/TSC2 heterodimer, acting as a brake downstream of Akt and upstream of mTOR. In the absence of the TSC1/TSC2 brake, mTOR activity is unleashed to inhibit Akt via an inhibitory feedback mechanism. Two recent studies used mouse genetics to assess the roles of PTEN and TSC2 in cancer, underscoring the importance of Akt-mTOR interplay for cancer progression and therapy.
Hay
Nissim
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Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, 60607, USA. nhay@ulc.edu
D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
D020558:GTP Phosphohydrolases; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; C494918:AKT1 protein, human