Giancotti Filippo G
Cell Biology Program, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 216, New York, NY 10021, USA.
Trends Pharmacol Sci. 2007 Oct;28(10):506-11. doi: 10.1016/j.tips.2007.08.004. Epub 2007 Sep 5.
The integrins play key roles in the signaling networks that drive pathological angiogenesis and tumor progression. Integrin beta4 is a laminin receptor upregulated in tumor cells and angiogenic endothelial cells. Biochemical studies have indicated that beta4 combines with and enhances the signaling function of multiple receptor tyrosine kinases, including ErbB2, EGF-R and Met. Genetic studies have revealed that beta4 signaling promotes both angiogenesis and tumorigenesis. Here, I discuss the hypothesis that beta4 promotes both processes by amplifying receptor-tyrosine-kinase signaling. Therefore, I propose that a simultaneous blockade of beta4 and receptor-tyrosine-kinase signaling represents a rational approach to cancer and anti-angiogenic therapy.
整合素在驱动病理性血管生成和肿瘤进展的信号网络中发挥关键作用。整合素β4是一种在肿瘤细胞和血管生成内皮细胞中上调的层粘连蛋白受体。生化研究表明，β4与多种受体酪氨酸激酶结合并增强其信号功能，包括ErbB2、表皮生长因子受体（EGF-R）和Met。遗传学研究显示，β4信号传导促进血管生成和肿瘤发生。在此，我讨论β4通过放大受体酪氨酸激酶信号传导促进这两个过程的假说。因此，我提出同时阻断β4和受体酪氨酸激酶信号传导是一种合理的癌症和抗血管生成治疗方法。
