Diverse mechanisms of AKT pathway activation in human malignancy

Mitchell Cheung, Joseph R. Testa

Research output: Contribution to journalReview articlepeer-review

151 Scopus citations

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.

Original languageEnglish
Pages (from-to)234-244
Number of pages11
JournalCurrent Cancer Drug Targets
Volume13
Issue number3
DOIs
StatePublished - 2013

Keywords

  • AKT/PKB kinases
  • Hemimegalencephaly
  • Human malignancy
  • Hypoglycemia
  • Oncogenes
  • Proteus syndrome
  • Targeted therapies
  • Tumor suppressor genes

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