Signaling adaptor protein Crk is indispensable for malignant feature of glioblastoma cell line KMG4

Signaling adaptor protein Crk is indispensable for malignant feature of glioblastoma cell line KMG4
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DOI:
10.1016/j.bbrc.2007.08.106
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发表时间:
2007-11-03
影响因子:
3.1
通讯作者:
Tanaka, Shinya
Tanaka, Shinya
中科院分区:
生物学4区
文献类型:
--
作者:
Wang, Lei;Tabu, Kouichi;Tanaka, Shinya

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信号接头蛋白Crk已被证明参与了包括脑肿瘤在内的人类癌症的发病机制,其中Crk被报道过表达。在这项研究中,我们探讨了Crk是否在脑肿瘤的恶性表型中不可或缺。在20例胶质瘤手术标本中,发现恶性肿瘤中CrkI和CrkII 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,发现细胞对层粘连蛋白的早期粘附受到抑制。伤口愈合实验显示,Crk敲低细胞的细胞运动性下降,并且这些细胞的锚定依赖性和非依赖性生长均受到抑制。此外,体内肿瘤形成潜能也明显受到抑制。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。(C) 2007爱思唯尔公司版权所有。
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. (C) 2007 Elsevier Inc. All rights reserved.