Mechanisms of ErbB receptor negative regulation and relevance in cancer.
Mechanisms of ErbB receptor negative regulation and relevance in cancer.
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DOI：
10.1016/j.yexcr.2008.07.022
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发表时间：
2009-02-15
影响因子：
3.7
通讯作者：
Carraway KL 3rd
中科院分区：
文献类型：
--
作者：
Fry WH;Kotelawala L;Sweeney C;Carraway KL 3rd
受体酪氨酸激酶的ErbB家族参与多种信号传导途径，这些信号传导途径共同指导控制成人发育和组织维持期间器官发生的转录程序。这些受体也经常被发现在各种癌症中过度表达或异常激活，这表明ErbB受体信号传导活性必须受到非常严格的调控。例如，足够水平的ErbB信号传导对于介导组织稳态是必要的，但是过度信号传导可以触发有助于癌症起始或进展的细胞过程。在过去的四分之一世纪的努力已经导致了一个彻底的理解，这些受体激活的信号通路和ErbB受体参与这些途径的机制。然而，负责衰减受体激活的补偿性负调控机制最近才开始探索。在这里，我们回顾了不同的已知机制的ErbB负调控，特别强调那些蛋白质，表现出一定的特异性的ErbB家族。我们还描述了ErbB负调控因子的丢失或抑制如何促进肿瘤的发展，并讨论了这些途径的恢复或增强如何代表ErbB靶向治疗发展的新途径。
The ErbB family of receptor tyrosine kinases engages a wide variety of signaling pathways that collectively direct transcriptional programs controlling organogenesis during development and tissue maintenance in the adult. These receptors are also frequently found overexpressed or aberrantly activated in various cancers, suggesting that ErbB receptor signaling activity must be very tightly regulated. Sufficient levels of ErbB signaling are necessary to mediate tissue homeostasis, for example, but over-signaling can trigger cellular processes that contribute to cancer initiation or progression. Efforts over the last quarter century have led to a thorough understanding of the signaling pathways that are activated by these receptors and the mechanisms by which ErbB receptors engage these pathways. However, the compensatory negative regulatory mechanisms responsible for attenuating receptor activation have only more recently begun to be explored. Here we review the different known mechanisms of ErbB negative regulation, with particular emphasis on those proteins that exhibit some specificity for the ErbB family. We also describe how loss or suppression of ErbB negative regulators may contribute to tumor development, and discuss how restoration or augmentation of these pathways may represent a novel avenue for the development of ErbB-targeted therapies.
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