E-Cadherin/p120-Catenin and Tetraspanin Co-029 Cooperate for Cell Motility Control in Human Colon Carcinoma
E-Cadherin/p120-Catenin and Tetraspanin Co-029 Cooperate for Cell Motility Control in Human Colon Carcinoma
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DOI：
10.1158/0008-5472.can-09-4482
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发表时间：
2010-10-01
期刊：
影响因子：
11.2
通讯作者：
Boucheix, Claude
中科院分区：
文献类型：
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作者：
Greco, Celine;Bralet, Marie-Pierre;Boucheix, Claude
肿瘤的侵袭和转移是依赖细胞迁移的临床治疗的主要障碍。在这里，我们阐明了结肠癌细胞迁移的机制，支持细胞表面四跨膜蛋白Co-029（tspan 8），这是已知的有利于肿瘤的进展和转移。这种机制通过沉默E-钙粘蛋白或其相关的衔接分子p120-连环蛋白（p120 ctn）而被揭示，并且它涉及胶原结合整合素α（1）β（1）和α（2）β（1）之间的信号转换。通过化学交联和结肠癌的免疫组织学分析证明了E-钙粘蛋白和Co-029之间的直接相互作用。Co-029的高表达和p120 ctn的胞浆游离均与不良预后相关。只有当p120 ctn沉默时，抗体介导的Co-029破坏才严重降低细胞运动性，这表明Co-029靶向可能阻碍肿瘤进展。我们的研究结果定义了四跨膜蛋白Co-029作为癌细胞运动调节剂的功能，并揭示了与进展和转移有关的粘附信号网络。Cancer Res; 70（19）; 7674-83. (C)2010年AACR。
Tumor invasion and metastasis are major obstacles to clinical treatment that rely on cell migration. Here, we elucidate a mechanism of colon carcinoma cell migration that is supported by the cell surface tetraspanin Co-029 (tspan8), which is known to favor tumor progression and metastasis. This mechanism is unmasked by silencing of E-cadherin or its associated adapter molecule p120-catenin (p120ctn), and it involves a switch in signaling between the collagen-binding integrins alpha(1)beta(1) and alpha(2)beta(1). Direct interaction between E-cadherin and Co-029 was documented by chemical cross-linking and immunohistologic analysis of colon carcinomas. High expression of Co-029 and cytoplasmic delocalization of p120ctn were each associated with poor prognosis. Cell motility was reduced severely by antibody-mediated disruption of Co-029 only when p120ctn was silenced, suggesting that tumor progression may be hindered by Co-029 targeting. Our findings define a function for tetraspanin Co-029 as a modifier of cancer cell motility and reveal an adhesion signaling network implicated in progression and metastasis. Cancer Res; 70(19); 7674-83. (C) 2010 AACR.