Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers

Z Gastroenterol. 2005 Oct;43(10):1133-9. doi: 10.1055/s-2005-858638.

Abstract

The lipid kinase phosphoinositide 3-OH kinase (PI3K) and its downstream target Akt, also known as protein kinase B (PKB), are crucial effectors in oncogenic signaling induced by various receptor-tyrosine kinases. In recent years, data are accumulating that PI3K/Akt signaling components are frequently altered in a variety of human malignancies. This review summarizes the major effects of PI3K/Akt signaling on proliferation, survival and resistance to apoptosis, angiogenesis and cell motility in gastrointestinal cancers. In addition, activation of PI3K/Akt by various growth factors, the modulation of downstream targets by Akt-induced phosphorylation as well as novel treatment strategies targeting this pathway in gastrointestinal tumors are discussed.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular
  • Colonic Neoplasms
  • DNA Repair
  • Gastrointestinal Neoplasms* / drug therapy
  • Gastrointestinal Neoplasms* / genetics
  • Gastrointestinal Neoplasms* / metabolism
  • Gastrointestinal Neoplasms* / mortality
  • Humans
  • Immunohistochemistry
  • Leukemia, Experimental / metabolism
  • Liver Neoplasms
  • MAP Kinase Signaling System
  • Mice
  • Neoplasm Metastasis
  • Pancreatic Neoplasms
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • Stomach Neoplasms
  • Tumor Cells, Cultured

Substances

  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt