Abstract
Abstract Overexpression and abnormal glycosylation of the epithelial glycoprotein MUC1 in cancer cells promotes metastasis. We have identified CIN85 (Cbl-interacting protein 85 KDa), as a binding partner of MUC1 in tumors. MUC1/CIN85 complex is found in early as well as advanced clinical stages of breast, ovarian, colon and prostate cancers among others. Co-localization of MUC1 and CIN85 on invadopodia structures enhances invasion and migration of cancer cells. Our hypothesis is that preventing the formation or dissociating existing CIN85/MUC1 complexes may result in a less aggressive tumor by decreasing local invasion and preventing distant metastases. To test this hypothesis, we have already identified and tested two novel compounds that significantly reduce the association between hypoglycosylated form of MUC1 and CIN85, and at 10μM concentration drastically reduce the migratory activity of mouse and human epithelial cancer cells. Our preliminary data also suggest that dissociation of the MUC1 and CIN85 complex decreases expression of hypoglycosylated MUC1, restoring the expression of its normal, fully glycosylated form. We are currently investigating the MUC1/CIN85-dependent signaling pathway with a particular focus on the ability of CIN85 to modulate MUC1 glycosylation by controlling its plasma membrane-Golgi trafficking. Ongoing experiments in an in vivo mouse model will confirm the ability of these drug compounds to decrease tumor growth and metastasis and validate CIN85/MUC1 complex as a viable therapeutic target and support development and testing of more potent antagonists. Citation Format: Sandra Cascio, Jacque Faylo, Raahul Sriram, Anda Vlad, Carlos Camacho, Olivera J. Finn. Validation of hypoglycosylated MUC1-CIN85 protein-protein interaction as a new therapeutic target for prevention of cancer invasion and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4126. doi:10.1158/1538-7445.AM2017-4126
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