Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers.
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.
Michl
P
P
Abt. Innere Medizin I, Universitätsklinikum Ulm, Germany. patrick.michl@medizin.uni-ulm.de
Downward
J
J
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular; D003110:Colonic Neoplasms; D004260:DNA Repair; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D007942:Leukemia, Experimental / Q000378:metabolism; D008113:Liver Neoplasms; D020935:MAP Kinase Signaling System; D051379:Mice; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured
D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt