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癌细胞中的CDC25磷酸酶:关键角色?理想靶点?

CDC25 phosphatases in cancer cells: key players? Good targets?

作者信息

Boutros Rose, Lobjois Valérie, Ducommun Bernard

机构信息

LBCMCP-CNRS UMR5088, IFR109 Institut d'Exploration Fonctionnelle des Génomes, University of Toulouse, 118 route de Narbonne, 31062 Toulouse, France.

出版信息

Nat Rev Cancer. 2007 Jul;7(7):495-507. doi: 10.1038/nrc2169.

Abstract

Cell division cycle 25 (CDC25) phosphatases regulate key transitions between cell cycle phases during normal cell division, and in the event of DNA damage they are key targets of the checkpoint machinery that ensures genetic stability. Taking only this into consideration, it is not surprising that CDC25 overexpression has been reported in a significant number of human cancers. However, in light of the significant body of evidence detailing the stringent complexity with which CDC25 activities are regulated, the significance of CDC25 overexpression in a subset of cancers and its association with poor prognosis are proving difficult to assess. We will focus on the roles of CDC25 phosphatases in both normal and abnormal cell proliferation, provide a critical assessment of the current data on CDC25 overexpression in cancer, and discuss both current and future therapeutic strategies for targeting CDC25 activity in cancer treatment.

摘要

细胞分裂周期25(CDC25)磷酸酶在正常细胞分裂过程中调节细胞周期各阶段之间的关键转换,在DNA损伤时,它们是确保遗传稳定性的检查点机制的关键靶点。仅考虑这一点,大量人类癌症中报道有CDC25过表达就不足为奇了。然而,鉴于有大量证据详细说明了CDC25活性调控的严格复杂性,CDC25在一部分癌症中的过表达的意义及其与不良预后的关联难以评估。我们将聚焦于CDC25磷酸酶在正常和异常细胞增殖中的作用,对目前关于癌症中CDC25过表达的数据进行批判性评估,并讨论针对癌症治疗中靶向CDC25活性的当前和未来治疗策略。

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