Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052, Australia.
Curr Mol Med. 2013 Jan;13(1):3-12.
Signaling pathways play a critical role in the maintenance of cellular structure and function. These pathways can act together with synergistic or antagonistic outcome. Cooperative and integrative cellular communication networks, otherwise known as crosstalk can amplify signaling cascades. Here, we focus on receptor crosstalk in the context of cardiovascular pathologies, mainly involving the epidermal growth factor receptor (EGFR), a critical mediator of multiple receptor pathways in normal physiological and pathophysiological processes. Considerable experimental evidence suggests that the uncontrolled expression of EGFR contributes to tumorigenesis through inhibition of apoptosis, angiogenesis, anchorage-independent growth and tumor-associated inflammation. Abnormal activation of the intrinsic tyrosine kinase of EGFR through mutation or overexpression is observed in various human cancer types. On the other hand, the role of EGFR in vascular biology is not well understood. In cardiovascular pathologies, such as atherosclerosis and restenosis, vascular smooth muscle cells (SMCs) migrate and proliferate, contributing to neointima formation, whilst apoptosis may cause plaque instability. EGFR can be transactivated by numerous pathologic stimuli that regulate SMC behaviour. This review describes our current understanding of the role of EGFR in SMC biology and pathology.
信号通路在维持细胞结构和功能方面起着关键作用。这些途径可以协同或拮抗作用。合作和综合的细胞通讯网络，也称为串扰，可以放大信号级联。在这里，我们主要关注心血管病理学背景下的受体串扰，涉及表皮生长因子受体 (EGFR)，它是正常生理和病理生理过程中多种受体途径的关键介质。大量实验证据表明，EGFR 的不受控制表达通过抑制细胞凋亡、血管生成、锚定非依赖性生长和肿瘤相关炎症促进肿瘤发生。在各种人类癌症类型中观察到 EGFR 的内在酪氨酸激酶通过突变或过表达的异常激活。另一方面，EGFR 在血管生物学中的作用尚不清楚。在心血管病理学中，如动脉粥样硬化和再狭窄，血管平滑肌细胞 (SMC) 迁移和增殖，导致新生内膜形成，而细胞凋亡可能导致斑块不稳定。EGFR 可以被调节 SMC 行为的许多病理刺激物转激活。这篇综述描述了我们目前对 EGFR 在 SMC 生物学和病理学中的作用的理解。
