Regulation and modulation of PTEN activity.

PTEN (Phosphatase and tensin homolog deleted on chromosome ten) is a tumor suppressor that is frequently mutated in most human cancers. PTEN is a lipid and protein phosphatase that antagonizes PI3K/AKT pathway through lipid phosphatase activity at the plasma membrane. More recent studies showed that, in addition to the putative role of PTEN as a PI(3,4,5)P3 3-phosphatase, it is a PI(3,4)P2 3-phosphatase during stimulation of class I PI3K signaling pathway by growth factor. Although PTEN tumor suppressor function via it's lipid phosphatase activity occurs primarily in the plasma membrane, it can also be found in the nucleus, in cytoplasmic organelles and extracellular space. PTEN has also shown phosphatase independent functions in the nucleus. PTEN can exit from the cell through exosomal export or secretion and has a tumor suppressor function in adjacent cells. PTEN has a critical role in growth, the cell cycle, protein synthesis, survival, DNA repair and migration. Understanding the regulation of PTEN function, activity, stability, localization and its dysregulation outcomes and also the intracellular and extracellular role of PTEN and paracrine role of PTEN-L in tumor cells as an exogenous therapeutic agent can help to improve clinical conceptualization and treatment of cancer.