Gotoh Noriko
Division of Systems Biomedical Technology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
Int J Biochem Cell Biol. 2009 Mar;41(3):511-5. doi: 10.1016/j.biocel.2008.06.019. Epub 2008 Aug 9.
The epidermal growth factor receptor family tyrosine kinases transduce signals for cell proliferation and migration and contribute to tumorigenesis. A recent extensive research has highlighted the major roles of the negative regulators of complex epidermal growth factor receptor signaling networks. These regulators fine-tune signaling under physiological conditions. When their expression is downregulated, the resultant aberrant epidermal growth factor receptor signaling may promote cell proliferation and migration, leading to increased tumorigenesis. In this paper, I review specific feedback inhibitors that target epidermal growth factor receptors preferentially, via multiple modes of action. The inhibitors include mitogen-inducible gene-6 (Mig-6)/receptor-associated late transducer (RALT)/Gene 33, fibroblast growth factor receptor substrate 2beta (FRS2beta)/suc1-associated neurotrophic factor target-2 (SNT-2)/FRS3, suppressor of cytokine signaling 3 (SOCS3)/SOCS4/SOCS5, and leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1). Although only fragmentary evidence is available regarding these inhibitors, they might be useful as cancer biomarkers, and the development of drugs that target them would certainly advance personalized medicine in the near future.
表皮生长因子受体家族酪氨酸激酶可转导细胞增殖和迁移信号，并促进肿瘤发生。最近的广泛研究突出了复杂的表皮生长因子受体信号网络负调控因子的主要作用。这些调控因子在生理条件下对信号进行微调。当它们的表达下调时，由此产生的异常表皮生长因子受体信号可能促进细胞增殖和迁移，导致肿瘤发生增加。在本文中，我将综述通过多种作用模式优先靶向表皮生长因子受体的特定反馈抑制剂。这些抑制剂包括丝裂原诱导基因-6（Mig-6）/受体相关晚期转导子（RALT）/基因33、成纤维细胞生长因子受体底物2β（FRS2β）/与suc1相关的神经营养因子靶标-2（SNT-2）/FRS3、细胞因子信号转导抑制因子3（SOCS3）/SOCS4/SOCS5以及富含亮氨酸重复序列和免疫球蛋白样结构域1（LRIG1）。尽管关于这些抑制剂仅有零碎的证据，但它们可能作为癌症生物标志物有用，并且靶向它们的药物开发在不久的将来肯定会推动个性化医疗的发展。
