PI3K/PTEN signaling in tumorigenesis and angiogenesis

Biochim Biophys Acta. 2008 Jan;1784(1):150-8. doi: 10.1016/j.bbapap.2007.09.008. Epub 2007 Sep 29.

Abstract

The phosphatidyl inositol 3-kinase (PI3K) can be activated by a variety of extracellular signals and involved in a number of cellular processes including cell proliferation, survival, protein synthesis, and tumor growth. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is an antagonist of PI3K. The alterations of PI3K pathway such as activation of oncogenes, gene amplification, and inactivation of tumor suppressors, commonly occur in many human cancers. Angiogenesis is required for tumor growth and metastasis when the tumor reaches more than 1 mm in diameter. Recent studies have shown that PI3K and Akt play an important role in regulating tumor growth and angiogenesis through VEGF and HIF-1 expression. PI3K regulates the expression of these two proteins through HDM2 and p70S6K1 in human cancer cells. The frequent dysregulation of the PI3K/PTEN pathway in human cancer demonstrates that this pathway is an appropriate target for cancer therapeutics. In this review, we describe the recent advances in understanding the PI3K/PTEN pathway, the role and mechanism of PI3K in regulating tumor growth and angiogenesis, and the potential therapeutic opportunities for targeting this pathway for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Enzyme Activation
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mutation
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Oncogenes
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Intercellular Signaling Peptides and Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human