Loss of E-Cadherin-Dependent Cell-Cell Adhesion and the Development and Progression of Cancer
Loss of E-Cadherin-Dependent Cell-Cell Adhesion and the Development and Progression of Cancer
复制标题
DOI：
10.1101/cshperspect.a029330
复制
发表时间：
2018-03-01
影响因子：
7.2
通讯作者：
Derksen, Patrick W. B.
中科院分区：
文献类型：
--
作者：
Bruner, Heather C.;Derksen, Patrick W. B.
经典钙粘蛋白是控制细胞间粘附的关键分子。尽管有这种功能，但也很明显，经典的钙粘蛋白不仅仅是将细胞保持在一起的“胶水”。钙粘蛋白是组织稳态的重要调节因子，通过将粘附信号转导至信号效应器和转录程序的复杂网络来控制细胞功能和发育的多个方面。在癌症中，钙粘蛋白通常被灭活或功能性抑制，导致疾病发展和/或进展。本文就E-钙粘蛋白及其在乳腺癌和胃癌发生发展中的作用作一综述。我们提供了一个生物化学后果的总结，并考虑在癌症中的早期（突变）E-钙粘蛋白损失的概念影响。我们主张，由E-钙粘蛋白损失驱动的癌症应被视为“肌动蛋白疾病”，由E-钙粘蛋白-肌动蛋白连接的特异性破坏和随后依赖于持续的肌动球蛋白收缩肿瘤进展引起。基于小鼠和人类研究的可用数据，我们讨论了有针对性的临床干预的机会。
Classical cadherins are the key molecules that control cell-cell adhesion. Notwithstanding this function, it is also clear that classical cadherins are more than just the "glue" that keeps the cells together. Cadherins are essential regulators of tissue homeostasis that govern multiple facets of cellular function and development, by transducing adhesive signals to a complex network of signaling effectors and transcriptional programs. In cancer, cadherins are often inactivated or functionally inhibited, resulting in disease development and/or progression. This review focuses on E-cadherin and its causal role in the development and progression of breast and gastric cancer. We provide a summary of the biochemical consequences and consider the conceptual impact of early (mutational) E-cadherin loss in cancer. We advocate that carcinomas driven by E-cadherin loss should be considered "actin-diseases," caused by the specific disruption of the E-cadherin-actin connection and a subsequent dependence on sustained actomyosin contraction for tumor progression. Based on the available data from mouse and human studies we discuss opportunities for targeted clinical intervention.