PTEN and the PI3-kinase pathway in cancer.

PTEN and the PI3-kinase pathway in cancer.
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DOI:
10.1146/annurev.pathol.4.110807.092311
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发表时间:
2009
期刊:
Annual review of pathology
影响因子:
--
通讯作者:
Baker SJ
Baker SJ
中科院分区:
其他
文献类型:
--
作者:
Chalhoub N;Baker SJ

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PI3-激酶和PTEN分别是PI3-激酶途径的主要正调节剂和负调节剂,其调节生长、存活和增殖。这些关键的信号传导组分是人类癌症中最常突变的两种蛋白质,导致PI3K信号传导的不受调节的激活,并为该途径在肿瘤发生中的中心作用提供了无可辩驳的遗传证据。PTEN通过使脂质信号传导中间体PIP3去磷酸化来调节PI3K信号传导,但PTEN可能具有额外的磷酸酶非依赖性活性,以及细胞核中的其他功能。在这篇综述中,我们强调了目前的工作,显示癌症相关的复杂性,在调节PTEN和PI3K活性,潜在的新功能,PTEN,和反馈调节的途径。PI3K信号转导的重要性和复杂性使其成为重要但具有挑战性的癌症治疗靶点。
PI3-kinase and PTEN are major positive and negative regulators, respectively, of the PI3-kinase pathway, which regulates growth, survival, and proliferation. These key signaling components are two of the most frequently mutated proteins in human cancers, resulting in unregulated activation of PI3K signaling and providing irrefutable genetic evidence of the central role of this pathway in tumorigenesis. PTEN regulates PI3K signaling by dephosphorylating the lipid signaling intermediate PIP3, but PTEN may have additional phosphatase-independent activities, as well as other functions in the nucleus. In this review, we highlight current work showing cancer-relevant complexities in the regulation of PTEN and PI3K activity, potential novel functions for PTEN, and feedback regulation within the pathway. The significance and complexity of PI3K signaling make it an important but challenging therapeutic target for cancer.
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