PI(3)King Apart PTEN's Role in Cancer
PI(3)King Apart PTEN's Role in Cancer
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DOI：
10.1158/1078-0432.ccr-09-2990
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发表时间：
2010-09-01
影响因子：
11.5
通讯作者：
Yu, Dihua
中科院分区：
文献类型：
--
作者：
Zhang, Siyuan;Yu, Dihua
肿瘤抑制磷酸酶和紧张素同源物（PTEN）是一种非冗余磷酸酶，可抑制最关键的促癌途径之一：磷脂酰肌醇3-激酶(PI3K)/Akt信号通路。除了磷脂酰肌醇-3,4,5-三磷酸（PIP3）去磷酸化的典型功能外，最近的研究表明，PTEN在调节基因组不稳定性、DNA修复、干细胞自我更新、细胞衰老以及细胞迁移和/或转移方面发挥着有趣的作用。临床上，PTEN突变和缺陷在许多类型的人类癌症中普遍存在。严重的PTEN缺乏还与肿瘤晚期和治疗耐药有关，例如抗her2治疗曲妥珠单抗耐药。目前，靶向失调的PI3K/PTEN-Akt信号轴已成为抗癌药物开发的主要原则之一。在这篇综述中，我们重点介绍了我们目前对PTEN功能的了解以及在剖析PTEN信号通路方面的最新发现。本文还讨论了PTEN在肿瘤中的解除调控、临床经验以及合理设计PI3K/ akt靶向治疗有效治疗肿瘤的新前景。临床癌症研究；16 (17);4325 - 30。(c) 2010年aacr。
The tumor suppressor phosphatase and tensin homolog (PTEN) is a nonredundant phosphatase, counteracting one of the most critical cancer-promoting pathways: the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. In addition to the canonical function of dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate (PIP3), recent studies showed the intriguing roles of PTEN in regulating genomic instability, DNA repair, stem cell self-renewal, cellular senescence, and cell migration and/or metastasis. Clinically, PTEN mutations and deficiencies are prevalent in many types of human cancers. Severe PTEN deficiency is also associated with advanced tumor stage and therapeutic resistance, such as the resistance to trastuzumab, an anti-HER2 therapy. Currently, targeting the deregulated PI3K/PTEN-Akt signaling axis has emerged as one of the major tenets in anticancer drug development. In this review, we highlight our current knowledge of PTEN function and the recent discoveries in dissecting the PTEN signaling pathway. The de-regulations of PTEN in cancers, clinical lessons, and new prospects of rationally designed PI3K/Akt-targeted therapy for effective cancer treatment are also discussed. Clin Cancer Res; 16(17); 4325-30. (C) 2010 AACR.