Dearth Robert K, Cui Xiaojiang, Kim Hyun-Jung, Hadsell Darryl L, Lee Adrian V
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Cell Cycle. 2007 Mar 15;6(6):705-13. doi: 10.4161/cc.6.6.4035. Epub 2007 Mar 20.
Insulin receptor substrates (IRSs) are adaptor proteins that link signaling from upstream activators to multiple downstream effectors to modulate normal growth, metabolism, survival, and differentiation. Recent cell culture studies have shown that IRSs can interact with, and are functionally required for, the transforming ability of many oncogenes. Consistent with this, IRSs are elevated and hyperactive in many human tumors. IRSs respond to many extracellular signals that are critical for mammary gland development, and we have shown that IRSs disrupt normal mammary acini formation in vitro, and cause mammary tumorigenesis and metastasis in vivo. In this review we will discuss the role of IRSs in both transformation and cancer progression.
胰岛素受体底物（IRSs）是衔接蛋白，可将上游激活因子的信号传导至多个下游效应器，从而调节正常的生长、代谢、存活和分化。最近的细胞培养研究表明，IRSs能够与许多癌基因的转化能力相互作用，并且是其功能所必需的。与此一致的是，IRSs在许多人类肿瘤中表达升高且过度活跃。IRSs对许多对乳腺发育至关重要的细胞外信号作出反应，并且我们已经表明，IRSs在体外破坏正常乳腺腺泡形成，并在体内导致乳腺肿瘤发生和转移。在本综述中，我们将讨论IRSs在转化和癌症进展中的作用。
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