Wang Lei, Tabu Kouichi, Kimura Taichi, Tsuda Masumi, Linghu Hua, Tanino Mishie, Kaneko Sadao, Nishihara Hiroshi, Tanaka Shinya
Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan, and Department of Obstetrics & Gynecology, First Affiliated Hospital of Chongqing University of Medical Sciences, China.
Biochem Biophys Res Commun. 2007 Nov 3;362(4):976-81. doi: 10.1016/j.bbrc.2007.08.106. Epub 2007 Aug 27.
Signaling adaptor protein Crk has been shown to be involved in pathogenesis of human cancers including brain tumor where Crk was reported to be overexpressed. In this study, we addressed whether Crk is indispensable for malignant phenotype of brain tumor. In 20 surgical specimens of glioma, mRNA of both CrkI and CrkII was found to be elevated in malignant tumor. To define a precise role of Crk, we have established Crk-knockdown cell lines of glioblastoma KMG4 by siRNA, and early phase of cell adhesion to laminin was found to be suppressed. Wound healing assay revealed the decreased cell motility in Crk knockdown cells, and suppression of both anchorage-dependent and -independent growth were demonstrated in these cells. Furthermore, in vivo tumor forming potential was also markedly suppressed. These results suggest that Crk is required for early attachment to laminin, cell motility, and growth of glioblastoma cell line KMG4.
信号衔接蛋白Crk已被证明参与包括脑肿瘤在内的人类癌症的发病机制，据报道在脑肿瘤中Crk过表达。在本研究中，我们探讨了Crk对于脑肿瘤恶性表型是否不可或缺。在20例胶质瘤手术标本中，发现恶性肿瘤中CrkI和CrkII的mRNA均升高。为了确定Crk的确切作用，我们通过siRNA建立了胶质母细胞瘤KMG4的Crk敲低细胞系，发现细胞与层粘连蛋白早期粘附阶段受到抑制。伤口愈合试验显示Crk敲低细胞的细胞运动性降低，并且在这些细胞中证明了锚定依赖性和非依赖性生长均受到抑制。此外，体内肿瘤形成潜力也明显受到抑制。这些结果表明，Crk是胶质母细胞瘤细胞系KMG4早期附着于层粘连蛋白、细胞运动和生长所必需的。
