Roles for crk in cancer metastasis and invasion.
Roles for crk in cancer metastasis and invasion.
复制标题
DOI：
10.1177/1947601912458687
复制
发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Tanaka, Shinya
中科院分区：
文献类型：
--
作者：
Tsuda, Masumi;Tanaka, Shinya
Crk家族的衔接子涉及调节各种生物学和病理学过程，如细胞增殖、粘附、迁移、侵袭、吞噬作用和存活。大量研究表明，Crk在人类肿瘤的侵袭性和恶性行为中起重要作用。在免疫组化分析和基因表达谱中，Crk的表达增强已在肺、乳腺和胃的腺癌以及肉瘤和神经胶质瘤中被确定。Crk在肿瘤细胞中的过表达通过Src家族酪氨酸激酶诱导支架分子如p130（Cas）和桩蛋白的显著酪氨酸磷酸化，并刺激细胞内信号传导的激活环，最终有助于癌细胞运动性和侵袭潜力的增加。因此，Crk蛋白不仅仅是细胞内信号传导的管道，而且还可以控制信号传导的幅度。本文综述了Crk及其介导的信号通路在肿瘤转移和侵袭中的作用，并探讨了其作为肿瘤治疗靶点的可能性。
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.