Death pathways triggered by activated Ras in cancer cells.
Death pathways triggered by activated Ras in cancer cells.
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DOI：
10.2741/3814
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Maltese WA
中科院分区：
文献类型：
--
作者：
Overmeyer JH;Maltese WA
Ras GTP酶以其作为调节细胞生长、分化和存活的分子开关的能力而闻名。在动物模型和人类中，导致Ras蛋白组成型活性形式表达的基因突变已明确与肿瘤发生相关。然而，在过去的二十年中，证据逐渐积累，以支持一个矛盾的作用Ras蛋白在启动细胞死亡途径。Ras在细胞增殖/存活与细胞死亡中的相反功能之间的平衡对于确定癌细胞的总体命运可能是至关重要的。在这篇综述中，我们将调查的文献，指出激活的Ras蛋白的能力，向细胞死亡的条件下，癌细胞遇到不利的环境条件下，或受到凋亡刺激的规模倾斜。在某些情况下，Ras激活的结果是通过与已知的效应子和明确的凋亡死亡途径的相互作用介导的。然而，在其他情况下，Ras似乎是通过触发新的非凋亡死亡机制来运作的，这些机制刚刚开始被表征。了解这些途径的细节，以及将Ras信号传导的性质从促生存变为促死亡的各种因素，可能为开发旨在操纵癌症中促死亡Ras效应途径的新型治疗方法奠定基础。
Ras GTPases are best known for their ability to serve as molecular switches regulating cell growth, differentiation and survival. Gene mutations that result in expression of constitutively active forms of Ras proteins have been clearly linked to oncogenesis in animal models and humans. However, over the past two decades, evidence has gradually accumulated to support a paradoxical role for Ras proteins in the initiation of cell death pathways. The balance between the opposing functions of Ras in cell proliferation/survival versus cell death can be critical for determining the overall fate of the cancer cell. In this review we will survey the body of literature that points to the ability of activated Ras proteins to tip the scales toward cell death under conditions where cancer cells encounter adverse environmental conditions or are subjected to apoptotic stimuli. In some cases the consequences of Ras activation are mediated through interactions with known effectors and well defined apoptotic death pathways. However, in other cases it appears that Ras operates by triggering novel non-apoptotic death mechanisms that are just beginning to be characterized. Understanding the details of these pathways, and the various factors that go into changing the nature of Ras signaling from pro-survival to pro-death, could potentially set the stage for the development of novel therapeutic approaches aimed at manipulating the pro-death Ras effector pathways in cancers.
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影响因子：
64.8
作者：
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通讯作者：
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