Non-canonical function of nuclear PTEN and its implication on tumorigenesis

Suppression of genomic instability is the key to prevent tumor development. PTEN is a unique tumor suppressor protein having both lipid and protein phosphatase activities. Interestingly though it is a cytoplasmic protein, but a significant pool of PTEN can also be localized in nucleus. The function of cytoplasmic PTEN is well defined and extensively studied in various literatures focusing mainly on the negative regulation of oncogenic PI-3Kinase-AKT pathway but functional regulation of nuclear PTEN is less defined and therefore it is a fascinating subject of research in cancer biology. Post-translation modulation of PTEN such as phosphorylation, sumorylation, acetylation and methylation also regulates its cellular localization, protein-protein association and catalytic function. Loss or mutation in PTEN is associated with the development of tumors in various tissues from the brain to prostate. Here we have summarized the role of nuclear PTEN and its epigenetic modulation in various DNA metabolic pathways, for example, DNA damage response, DNA repair, DNA replication, DNA segregation etc. Further, pathways involved in nuclear PTEN degradation are also discussed. Additionally, we also emphasize probable potential targets associated with PTEN pathway for chemotherapeutic purpose.