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.

抑制基因组不稳定性是预防肿瘤发展的关键。 PTEN 是一种独特的肿瘤抑制蛋白，具有脂质和蛋白磷酸酶活性。有趣的是，虽然它是一种细胞质蛋白，但大量 PTEN 也可以定位于细胞核中。细胞质 PTEN 的功能已得到明确定义，并在各种文献中进行了广泛研究，主要集中于致癌 PI-3 激酶 -AKT 通路的负调节，但核 PTEN 的功能调节定义较少，因此它是癌症生物学研究的一个令人着迷的课题。 PTEN 的翻译后调节，如磷酸化、苏莫化、乙酰化和甲基化，也调节其细胞定位、蛋白质-蛋白质关联和催化功能。 PTEN 的丢失或突变与从大脑到前列腺等各种组织中肿瘤的发生有关。在这里，我们总结了核PTEN的作用及其在各种DNA代谢途径中的表观遗传调节，例如DNA损伤反应、DNA修复、DNA复制、DNA分离等。此外，还讨论了核PTEN降解所涉及的途径。此外，我们还强调与用于化疗目的的 PTEN 通路相关的可能潜在靶点。