title: Diverse mechanisms of AKT pathway activation in human malignancy.
abstract: AKT/PKB (Protein Kinase B) are central proteins mediating signals from receptor tyrosine kinases and phosphatidylinositol 3-kinase. AKT kinases are involved in a number of important cellular processes including cell proliferation and survival, cell size in response to nutrient availability, tumor invasion/metastasis, and angiogenesis.Various components of the AKT signaling pathway are encoded by tumor suppressor genes and oncogenes whose loss or activation, respectively, plays an important role in tumorigenesis. The growing body of evidence connecting deregulated AKT signaling with sporadic human cancers and inherited cancer predisposition syndromes is discussed. We also highlight new findings regarding the involvement of activating mutations of AKT1, AKT2, and AKT3 in somatic overgrowth disorders: Proteus syndrome, hypoglycemia with hypertrophy, and hemimegalencephaly, respectively. In addition, we review recent literature documenting the various ways the AKT signaling pathway is activated in human cancers and consequences for molecularly targeted therapies.
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Cheung
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000819:agonists / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009363:Neoplasm Proteins; D051057:Proto-Oncogene Proteins c-akt