PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control.
PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control.
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DOI：
10.1177/1947601911407325
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发表时间：
2010-12-01
期刊：
影响因子：
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通讯作者：
Georgescu, Maria-Magdalena
中科院分区：
文献类型：
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作者：
Georgescu, Maria-Magdalena
PI3K-Akt 通路是癌症中激活的主要生存通路。开发靶向治疗的努力尚未完全成功，主要是因为广泛的内部通路内或外部通路间负反馈环路或通路抑制因子之间的网络。 PTEN 肿瘤抑制因子是该通路的主要制动器，也是体细胞癌失活的常见靶点。本综述将重点介绍 PTEN 与其他与癌症进展相关的途径抑制剂的网络。 PTEN 构成抑制网络的主要节点，将从生长因子受体开始，描述 PI3K-Akt 通路中不同级别的一系列汇聚。由于 PTEN 作为磷脂酰肌醇-3,4,5-三磷酸 (PIP(3)) 磷酸酶发挥酶活性，从而对抗 PI3K 的活性，因此将讨论依靠其他磷酸肌醇酶或其他分子对 PTEN 活性的内在调节来增加癌细胞中 PIP(3) 可用性的协同作用。特别是，将提出 PTEN 与其直接相互作用蛋白环之间的协同作用，以试图了解 PI3K-Akt 途径的激活以及与其他平行致癌途径的联系。对癌症中 PI3K-Akt 通路调节剂之间相互作用的理解最终将有助于设计出提高临床疗效的治疗方法。
The PI3K-Akt pathway is a major survival pathway activated in cancer. Efforts to develop targeted therapies have not been fully successful, mainly because of extensive internal intrapathway or external interpathway negative feedback loops or because of networking between pathway suppressors. The PTEN tumor suppressor is the major brake of the pathway and a common target for inactivation in somatic cancers. This review will highlight the networking of PTEN with other inhibitors of the pathway, relevant to cancer progression. PTEN constitutes the main node of the inhibitory network, and a series of convergences at different levels in the PI3K-Akt pathway, starting from those with growth factor receptors, will be described. As PTEN exerts enzymatic activity as a phosphatidylinositol-3,4,5-trisphosphate (PIP(3)) phosphatase, thus opposing the activity of PI3K, the concerted actions to increase the availability of PIP(3) in cancer cells, relying either on other phosphoinositide enzymes or on the intrinsic regulation of PTEN activity by other molecules, will be discussed. In particular, the synergy between PTEN and the circle of its direct interacting proteins will be brought forth in an attempt to understand both the activation of the PI3K-Akt pathway and the connections with other parallel oncogenic pathways. The understanding of the interplay between the modulators of the PI3K-Akt pathway in cancer should eventually lead to the design of therapeutic approaches with increased efficacy in the clinic.