Tsuda Masumi, Tanaka Shinya
Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Genes Cancer. 2012 May;3(5-6):334-40. doi: 10.1177/1947601912458687.
The Crk family of adaptors is implicated in regulating various biological and pathological processes such as cell proliferation, adhesion, migration, invasion, phagocytosis, and survival. A large number of studies have shown that Crk plays an important role in aggressive and malignant behaviors of human cancers. In immunohistochemical analyses and gene-expression profiles, enhanced expression of Crk has been identified in adenocarcinomas of lung, breast, and stomach and in sarcomas and glioma. Overexpression of Crk in tumor cells induces the prominent tyrosine phosphorylations of scaffolding molecules such as p130(Cas) and paxillin through Src family tyrosine kinases and stimulates the activation loop of intracellular signalling, ultimately contributing to the increased motility and aggressive potential of cancer cells. Crk proteins thus are not simply conduits for intracellular signal transduction but also can control the amplitude of signalling. This review summarizes the significance of Crk and its mediated signaling assemblies, particularly in regulating tumor metastasis and invasion, and discusses the possibilities that they are potential cancer therapeutic targets.
衔接蛋白Crk家族参与调控多种生物学和病理过程，如细胞增殖、黏附、迁移、侵袭、吞噬作用和存活。大量研究表明，Crk在人类癌症的侵袭性和恶性行为中起重要作用。在免疫组织化学分析和基因表达谱中，已发现在肺癌、乳腺癌和胃癌的腺癌以及肉瘤和神经胶质瘤中Crk表达增强。肿瘤细胞中Crk的过表达通过Src家族酪氨酸激酶诱导支架分子如p130(Cas)和桩蛋白发生显著的酪氨酸磷酸化，并刺激细胞内信号转导的激活环，最终导致癌细胞运动性增加和侵袭潜能增强。因此，Crk蛋白不仅是细胞内信号转导的通道，还能控制信号转导的幅度。本综述总结了Crk及其介导的信号组装体的重要性，特别是在调节肿瘤转移和侵袭方面，并讨论了它们作为潜在癌症治疗靶点的可能性。
