Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis.
Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis.
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DOI：
10.3390/cancers7010342
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发表时间：
2015-02-10
期刊：
影响因子：
5.2
通讯作者：
Finn OJ
中科院分区：
文献类型：
--
作者：
Cascio S;Finn OJ
我们之前报道过 CIN85 是一种 85 KDa 的蛋白质，已知通过与 Cbl 相互作用参与肿瘤细胞迁移和转移，与肿瘤细胞中的 MUC1 相关。 MUC1/CIN85复合物还在体外调节肿瘤细胞的迁移和侵袭。在这里，我们通过免疫组织化学专门检查了人类结肠癌组织微阵列 (TMA) 中 MUC1 和 CIN85 的表达及其在癌症进展和转移中的潜在作用。我们检测到与晚期肿瘤分期和淋巴结转移相关的 MUC1 和 CIN85 表达显着增加。我们进一步研究了 Cbl 是否也存在于 MUC1/CIN85 复合物中。免疫共沉淀测定表明，Cbl 与 CIN85 和 MUC1 在人结肠癌细胞系中共定位。为了开始研究 MUC1 过表达的体内相关性以及与 CIN85 和 Cbl 在癌症发生和进展中的关联，我们使用在结肠上皮细胞上表达 MUC1 的人 MUC1 转基因小鼠，用氧化偶氮甲烷处理以启动并用葡聚糖硫酸钠 (AOM/DSS) 处理以促进结直肠癌发生。与野生型小鼠相比，MUC1.Tg 小鼠的肿瘤发生率更高，存活率更低。与体外数据一致，在 AOM/DSS 处理的 MUC1 转基因小鼠的结肠组织中检测到 MUC1、CIN85 和 Cbl 的关联。 MUC1/CIN85/Cbl 复合物似乎有助于结肠癌的促进和进展，因此早期结肠癌中 MUC1、CIN85 和 Cbl 表达的增加可能预示着不良预后。
We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis.
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影响因子：
--
作者：
Cascio S;Farkas AM;Hughey RP;Finn OJ
通讯作者：
Finn OJ
影响因子：
8
作者：
Schroeder, JA;Adriance, MC;Gendler, SJ
通讯作者：
Gendler, SJ
影响因子：
64.8
作者：
Soubeyran, P;Kowanetz, K;Dikic, I
通讯作者：
Dikic, I
影响因子：
3.7
作者：
Tanaka K;Arao T;Tamura D;Aomatsu K;Furuta K;Matsumoto K;Kaneda H;Kudo K;Fujita Y;Kimura H;Yanagihara K;Yamada Y;Okamoto I;Nakagawa K;Nishio K
通讯作者：
Nishio K
影响因子：
29.4
作者：
NAKAMORI, S;OTA, DM;IRIMURA, T
通讯作者：
IRIMURA, T