Overexpression of CRKII increases migration and invasive potential in oral squamous cell carcinoma
Overexpression of CRKII increases migration and invasive potential in oral squamous cell carcinoma
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DOI：
10.1016/j.canlet.2011.01.004
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发表时间：
2011-04-28
期刊：
影响因子：
9.7
通讯作者：
Nemoto, Takayuki K.
中科院分区：
文献类型：
--
作者：
Yamada, Shin-ichi;Yanamoto, Souichi;Nemoto, Takayuki K.
CT10调节蛋白(CRK)最初被鉴定为鸡CT10逆转录病毒系统中v-CRK的癌基因产物。据报道，CRKII在几种人类癌症中过表达。CRKII调控细胞的迁移、形态发生、侵袭、吞噬和存活；然而，其潜在的机制尚不清楚。在本研究中，我们评估了CRKII作为癌症基因治疗的合适分子靶点的可能性。应用免疫组织化学方法检测71例口腔鳞癌组织和10例正常口腔黏膜组织中CRKII的表达，并探讨其与临床病理因素的关系。70例口腔鳞状细胞癌中有41例CRKII过表达，高于正常口腔黏膜。此外，根据T分期、N分期和浸润性模式，CRKII过表达在高级别肿瘤中更为常见。此外，RNAi介导的CRKII表达抑制降低了口腔鳞状细胞癌细胞系OSC20的迁移和侵袭潜力。下调CRKII的表达也减少了Dock180、p130Cas和rac1以及肌动蛋白相关的支架蛋白Cortactin的表达。这些结果表明，CRKII的过度表达与口腔鳞癌的侵袭性表型密切相关。因此，我们认为CRKII可能成为RNAi靶向治疗口腔鳞状细胞癌的潜在分子靶点。皇冠版权所有(C)2011由爱思唯尔爱尔兰有限公司出版。保留所有权利。
CT10 regulator of kinase (CRK) was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of CRKII as an appropriate molecular target for cancer gene therapy. The expression of CRKII in 71 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of CRKII overexpression with clinicopathological factors was evaluated. Overexpression of CRKII was detected in 41 of 70 oral squamous cell carcinomas, the frequency being more significant than in normal oral mucosa. In addition, CRKII overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. Moreover, RNAi-mediated suppression of CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of CRKII expression also reduced the expression of Dock180, p130Cas, and Rac1, and the actin-associated scaffolding protein cortactin. These results indicate that the overexpression of CRKII is tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved.