Hsp90相互作用组与癌症发生之间 "黄昏地带 "的非同寻常嫌疑人

Advances in cancer research Pub Date : 2016-01-01 Epub Date: 2015-10-23 DOI:10.1016/bs.acr.2015.08.001
Evangelia Vartholomaiou, Pablo C Echeverría, Didier Picard
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引用次数: 42

摘要

自从发现癌细胞比正常细胞对 Hsp90 抑制更敏感以来,分子伴侣 Hsp90 就引起了癌症研究的极大兴趣。为什么会出现这种情况,至今仍是一个争论不休的问题。除了某些突变癌细胞蛋白对 Hsp90 的依赖性增加以及 Hsp90 机制本身的改变外,癌细胞的其他一些特征也可能导致了这种现象;这些特征包括非整倍体、缺陷蛋白和突变蛋白的总体数量和水平增加,这些都有助于扰乱蛋白稳态。过去二十年的研究表明,许多与癌症相关的蛋白质都是 Hsp90 的客户,但其中只有极少数蛋白质得到了广泛的研究,这些蛋白质或是因为具有明显的癌症驱动功能,或是因为被证明是监测 Hsp90 抑制剂效果的方便生物标记物。我们综述的目的是要超越这些 "常见疑点"。我们建立了一个工作流程,以选择与癌症过程相关且符合 Hsp90 客户条件的研究较少的蛋白质。通过讨论和重新审视这些 "不寻常的嫌疑人",我们希望能激励其他人将它们作为新的治疗靶点或诊断标志物重新审视。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unusual Suspects in the Twilight Zone Between the Hsp90 Interactome and Carcinogenesis.

The molecular chaperone Hsp90 has attracted a lot of interest in cancer research ever since cancer cells were found to be more sensitive to Hsp90 inhibition than normal cells. Why that is has remained a matter of debate and is still unclear. In addition to increased Hsp90 dependence for some mutant cancer proteins and modifications of the Hsp90 machinery itself, a number of other characteristics of cancer cells probably contribute to this phenomenon; these include aneuploidy and overall increased numbers and levels of defective and mutant proteins, which all contribute to perturbed proteostasis. Work over the last two decades has demonstrated that many cancer-related proteins are Hsp90 clients, and yet only few of them have been extensively investigated, selected either on the basis of their obvious function as cancer drivers or because they proved to be convenient biomarkers for monitoring the effects of Hsp90 inhibitors. The purpose of our review is to go beyond these "usual suspects." We established a workflow to select poorly studied proteins that are related to cancer processes and qualify as Hsp90 clients. By discussing and taking a fresh look at these "unusual suspects," we hope to stimulate others to revisit them as novel therapeutic targets or diagnostic markers.

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