Expression and function of the insulin receptor substrate proteins in cancer.
Expression and function of the insulin receptor substrate proteins in cancer.
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DOI：
10.1186/1478-811x-7-14
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发表时间：
2009-06-17
期刊：
影响因子：
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通讯作者：
Shaw LM
中科院分区：
文献类型：
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作者：
Mardilovich K;Pankratz SL;Shaw LM
胰岛素受体底物（IRS）蛋白是细胞质衔接蛋白，其作为活化的细胞表面受体下游的必需信号传导中间体起作用，其中许多与癌症有关。IRS蛋白不含任何内在激酶活性，而是作为骨架组织信号复合物并启动细胞内信号通路。IRS蛋白作为影响肿瘤进展的多种受体的共同中间体，在调节肿瘤细胞对许多不同微环境刺激的反应中发挥关键作用。对IRS在人类肿瘤中表达的有限研究以及对IRS在人类肿瘤细胞系和小鼠模型中功能的研究为这些衔接蛋白在人类癌症中的潜在功能提供了线索。这些研究产生了一个一般主题; IRS-1和IRS-4最常与肿瘤生长和增殖相关，IRS-2最常与肿瘤运动和侵袭相关。在这篇综述中，我们讨论了IRS的表达和功能的调节机制，以及IRS蛋白如何有助于肿瘤的发生和发展。
The Insulin Receptor Substrate (IRS) proteins are cytoplasmic adaptor proteins that function as essential signaling intermediates downstream of activated cell surface receptors, many of which have been implicated in cancer. The IRS proteins do not contain any intrinsic kinase activity, but rather serve as scaffolds to organize signaling complexes and initiate intracellular signaling pathways. As common intermediates of multiple receptors that can influence tumor progression, the IRS proteins are positioned to play a pivotal role in regulating the response of tumor cells to many different microenvironmental stimuli. Limited studies on IRS expression in human tumors and studies on IRS function in human tumor cell lines and in mouse models have provided clues to the potential function of these adaptor proteins in human cancer. A general theme arises from these studies; IRS-1 and IRS-4 are most often associated with tumor growth and proliferation and IRS-2 is most often associated with tumor motility and invasion. In this review, we discuss the mechanisms by which IRS expression and function are regulated and how the IRS proteins contribute to tumor initiation and progression.