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.