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PI3K/AKT/mTOR 交互途径。

The PI3K/AKT/mTOR interactive pathway.

作者信息

Ersahin Tulin, Tuncbag Nurcan, Cetin-Atalay Rengul

机构信息

Cancer Systems Biology Laboratory, Graduate School of Informatics, ODTU, 06800 Ankara, Turkey.

出版信息

Mol Biosyst. 2015 Jul;11(7):1946-54. doi: 10.1039/c5mb00101c.

Abstract

The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) signalling pathway is hyperactivated or altered in many cancer types and regulates a broad range of cellular processes including survival, proliferation, growth, metabolism, angiogenesis and metastasis. The PI3K/AKT/mTOR pathway is regulated by a wide-range of upstream signalling proteins and it regulates many downstream effectors by collaborating with various compensatory signalling pathways, primarily with RAF/MEK/ERK pathway. Limited clinical success of the available targeted therapeutic agents and challenges mediated by tumour heterogeneity across different cancer types emphasize the importance of alterations in the PI3K/AKT/mTOR pathway in the design of effective personalized treatment strategies. Here we report a comprehensive PI3K/AKT/mTOR network that represents the intricate crosstalk between compensatory pathways, which can be utilized to study the AKT signalling mechanism in detail and improve the personalized combinatorial therapeutic strategies.

摘要

磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素哺乳动物靶蛋白(mTOR)信号通路在多种癌症类型中被过度激活或改变,并调节包括存活、增殖、生长、代谢、血管生成和转移在内的广泛细胞过程。PI3K/AKT/mTOR通路受多种上游信号蛋白调节,并通过与各种补偿性信号通路(主要是RAF/MEK/ERK通路)协作来调节许多下游效应器。现有靶向治疗药物有限的临床成功以及不同癌症类型中肿瘤异质性介导的挑战,强调了PI3K/AKT/mTOR通路改变在有效个性化治疗策略设计中的重要性。在此,我们报告了一个全面的PI3K/AKT/mTOR网络,该网络代表了补偿性通路之间复杂的相互作用,可用于详细研究AKT信号机制并改进个性化联合治疗策略。

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