Targeting Cdc42 in cancer.

Targeting Cdc42 in cancer.
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DOI:
10.1517/14728222.2013.828037
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发表时间:
2013-11
影响因子:
5.8
通讯作者:
Chernoff J
Chernoff J
中科院分区:
医学2区
文献类型:
--
作者:
Arias-Romero LE;Chernoff J

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Rho GTP 酶是一个蛋白质家族,可控制响应细胞外刺激和内部程序的基本细胞过程。 Rho GTP 酶起到分子开关的作用,其中 GTP 结合蛋白具有活性,而 GDP 结合蛋白则无活性。本次综述将重点关注 Rho 家族的一个成员 Cdc42,它在多种人类癌症中过度表达,可能为恶性肿瘤提供新的治疗靶点。在这篇综述中,描述了 Cdc42 的关键调节子和效应子及其分子改变。还分析了 Cdc42 调节的信号级联之间的复杂相互作用。虽然人类癌症中尚未报道 Cdc42 突变,但已报道在多种肿瘤类型中存在 Cdc42 异常表达,并且在某些情况下与不良预后相关。最近,有研究表明,致癌 Ras 激活 Cdc42 对于 Ras 介导的肿瘤发生至关重要,这表明靶向 Cdc42 或其效应子可能对含有激活 Ras 突变的肿瘤有用。
The Rho GTPases are a family of proteins that control fundamental cellular processes in response to extracellular stimuli and internal programs. Rho GTPases function as molecular switches in which the GTP-bound proteins are active and GDP-bound proteins are inactive. This review will focus on one Rho family member, Cdc42, which is overexpressed in a number of human cancers, and which might provide new therapeutic targets in malignancies. In this review the key regulators and effectors of Cdc42 and their molecular alterations are described. The complex interactions between the signaling cascades regulated by Cdc42 are also analyzed. While mutations in Cdc42 have not been reported in human cancer, aberrant expression of Cdc42 has been reported in a variety of tumor types and in some instances has been correlated with poor prognosis. Recently, it has been shown that Cdc42 activation by oncogenic Ras is crucial for Ras-mediated tumorigenesis, suggesting that targeting Cdc42 or its effectors might be useful in tumors harboring activating Ras mutations.
DOI: 10.1158/0008-5472.can-12-4453
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