PTEN-Dependent Cell Cycle Arrest and Apoptosis Pathway

PTEN is a tumor suppressor gene. Recombinant PTEN is capable of dephosphorylating phosphatidylinositol 3,4,5-triphosphate[PI(3,4,5)P3], the product of phosphatidylinositol 3-kinase. Many of the cancer-related mutations have been mapped to the phosphatase catalytic domain; it has been suggested that the phosphatase activity of PTEN is required for its tumor suppressor function. The activation of PKB/AKT is regulated in a complex manner via phosphorylation of AKT on Thr308 and Ser473 by PDK1 and ILK (integrin-linked kinase) respectively. Inactivation of PTEN will constitutively activate PKB/AKT pathway. In addition to its role in regulating the PI 3-K/AKT cell survival pathway, PTEN also inhibits growth factor-induced Shc phosphorylation and suppresses the mitogen-activated protein (MAP) kinase signaling pathway. PTEN also interacts with FAK, a key molecule implicated in integrin signaling pathways, and it directly dephosphorylates tyrosine-phosphorylated FAK. PTEN down-regulation of p130CAS through FAK results in inhibition of cell migration and spreading. (NCI Thesaurus/BIOCARTA)

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