Expression and functional role of negative signalling regulators in tumour development and progression
Expression and functional role of negative signalling regulators in tumour development and progression
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DOI：
10.1002/ijc.25542
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发表时间：
2010-12-01
影响因子：
6.4
通讯作者：
Gnanapragasam, Vincent J.
中科院分区：
文献类型：
--
作者：
Murphy, Tania;Hori, Satoshi;Gnanapragasam, Vincent J.
细胞内信号通路（例如丝裂原激活蛋白激酶（MAPK））的改变是肿瘤发生和进展的关键常见机制。因此，人们对开发能够抑制或减弱细胞内信号传导的药物进行了大量研究。近年来，人们越来越认识到细胞已经具有先天的负调节蛋白，可以在正常的体内平衡中实现这一目标。这些调节器提供反馈抑制机制，控制外源刺激激活信号的强度和持续时间。该组的成员包括 Raf 激酶抑制剂蛋白 1、MAPK 磷酸酶、SPROUTY 和 SPRED 家族以及与 FGF 相似的表达。许多研究现已证明不同癌症类型的恶性组织中负调节因子的表达发生显着变化。在功能研究中，这些调节因子的操纵表达已被证明可以显着影响肿瘤细胞的行为和表型。在这里，我们总结了负信号调节因子在肿瘤生长和进展中功能表达的证据，并讨论了它们作为癌症生物标志物和新型药物治疗靶点的潜在作用。
Alterations in intracellular signalling pathways such as the mitogen-activated protein kinases (MAPKs) are key common mechanisms of tumour development and progression. As such, there has been intense research into developing drugs that can inhibit or attenuate intracellular signalling. In recent years, there has been increasing recognition that the cell already has innate negative regulatory proteins that achieve this in normal homeostasis. These regulators provide a feedback inhibitory mechanism that controls the intensity and duration of activated signalling by exogenous stimuli. Members of this group include Raf kinase inhibitor protein 1, the MAPK phosphatases, the SPROUTY and SPRED families and similar expression to FGF. A number of studies have now demonstrated significant alterations in expression of negative regulators in malignant tissue in different cancer types. In functional studies, manipulated expression of these regulators has been shown to significantly influence tumour cell behaviour and phenotype. Here, we summarise the evidence for the functional expression of negative signalling regulators in tumour growth and progression and discuss their potential role as cancer biomarkers and targets for novel drug therapy.