Department of Medicine, University of California at San Diego, La Jolla, California 92093.
Department of Pathology, University Medical Center Utrecht, Utrecht 3584CX, The Netherlands.
Cold Spring Harb Perspect Biol. 2018 Mar 1;10(3):a029330. doi: 10.1101/cshperspect.a029330.
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.
经典钙黏蛋白是控制细胞间黏附的关键分子。尽管具有这种功能，但经典钙黏蛋白显然不仅仅是将细胞“黏合”在一起的“胶水”。钙黏蛋白是组织稳态的必需调节剂，通过将黏附信号转导到一个复杂的信号效应器和转录程序网络，调节细胞功能和发育的多个方面。在癌症中，钙黏蛋白经常失活或功能受到抑制，导致疾病的发生和/或进展。本综述重点关注 E-钙黏蛋白及其在乳腺癌和胃癌发生和发展中的因果作用。我们总结了生化后果，并考虑了早期（突变）E-钙黏蛋白缺失在癌症中的概念影响。我们主张，由 E-钙黏蛋白缺失驱动的癌应被视为“肌动蛋白疾病”，这是由 E-钙黏蛋白-肌动蛋白连接的特定破坏以及随后对持续肌球蛋白收缩的依赖性引起的，这对于肿瘤进展是必需的。基于来自小鼠和人类研究的现有数据，我们讨论了靶向临床干预的机会。
