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Cancers 2015, 7(1), 342-352;

Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261, USA
Fondazione Ri.Med, via Bandiera, Palermo 90133, Italy
Authors to whom correspondence should be addressed.
Academic Editor: Scott A. Weed
Received: 15 October 2014 / Accepted: 3 February 2015 / Published: 10 February 2015
(This article belongs to the Special Issue Cancer Cell Invasion)
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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. View Full-Text
Keywords: MUC1/CIN85/Cbl complex; protein-protein interaction; lymph node metastasis MUC1/CIN85/Cbl complex; protein-protein interaction; lymph node metastasis

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Cascio, S.; Finn, O.J. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis. Cancers 2015, 7, 342-352.

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