Diverse Mechanisms of AKT Pathway Activation in Human Malignancy
Joseph R. Testa.
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.
Keywords: AKT/PKB kinases, hemimegalencephaly, human malignancy, hypoglycemia, oncogenes, proteus syndrome,
targeted therapies, tumor suppressor genes
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