Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma
Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma
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DOI：
10.1016/j.jhep.2004.06.018
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发表时间：
2004-10-01
影响因子：
25.7
通讯作者：
Hirohashi, S
中科院分区：
文献类型：
--
作者：
Chuma, M;Sakamoto, M;Hirohashi, S
背景/目的：肝细胞癌（HCC）转移的分子基础尚未完全了解。本研究的目的是阐明与肝癌转移相关的关键基因。方法：采用寡核苷酸芯片技术比较高转移肝癌细胞系和非转移肝癌细胞系的表达谱，筛选与转移相关的基因。我们进一步研究了所鉴定的基因在体外和体内对细胞运动和转移的影响。结果：共鉴定出39个基因，其表达水平与肿瘤转移能力显著相关（P < 0.05）。在这些基因中，我们进一步研究了皮质肌动蛋白，因为这种皮质肌动蛋白相关蛋白是Src的底物，Src的激活已被证明参与HCC细胞的迁移和转移。在非转移性HCC细胞系中corneumen的过表达增加了细胞运动性，并导致原位模型中的转移。免疫组化结果显示，coronin在有肝内转移的HCC中的表达显著高于无肝内转移的HCC（P
Background/Aims: The molecular basis of the metastasis of hepatocellular carcinoma (HCC) is not fully understood. The aim of this study was to elucidate the crucial genes involved in metastasis of HCC.Methods: We compared expression profiles among highly metastatic HCC cell lines and non-metastatic HCC cell lines by using oligonucleotide array to identify genes associated with metastasis. We further investigated the effect of identified gene on cell motility and metastasis in vitro and in vivo. Finally, we examined immunohistochemistry in human tissue samples.Results: We identified 39 genes whose expression levels were significantly correlated with metastatic ability (P < 0.05). Of these genes, we further investigated cortactin, because this cortical actin-associated protein is a substrate of Src, whose activation has been shown to be involved in HCC cell migration and metastasis. Overexpression of cortactin in a non-metastatic HCC cell line increased cell motility, and resulted in metastasis in an orthotopic model. Furthermore, immunohistochemical expression of cortactin revealed its significant overexpression in HCC with intrahepatic metastasis compared with HCC without intrahepatic metastasis (P