Mucins, epithelial differentiation and carcinogenesis




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The research developed by team 5 of JPARC aims at studying the role of membrane-bound mucins MUC1 and MUC4 in epithelial carcinogenesis. We also study the molecular mechanisms associated with tumor resistance and tumor dormancy (Participation to the ONCOLILLE SIRIC).

 

1- Role of MUC1 and MUC4 mucin (progression, metastasis) in pancreatic, oesophageal, colonic and renal carcinogenesis. In vitro (cell lines), in vivo (animal models) and ex vivo (patient material) studies.

2- Study of MUC4-ErbB2 and MUC1-EGFR complexes. Structure-function relationship. Identification of intracellular trafficking mechanisms (sorting). Role of galectins. Role of nuclear translocation of MUC1 cytoplasmic tail. Target genes?

3- Epigenetic regulation (DNA methylation, histone modifications) and regulation by miRNA of the 11p15 mucin genes and of MUC1 and MUC4 mucin genes in epithelial cancers (respiratory and digestive tracts). Application to the diagnosis/prognosis of epithelial tumors.

4- Mechanisms of chemoresistance and tumor dormancy. Cancer stem cells. Role of epigenetics (model of the intestinal crypt-villus axis).

5- Translational research with hospital partners. Mucins as diagnostic/prognostic factors for tumor identification/classification and as predictive factors for therapy orientation and patient management.