Rôle de MUC1 au cours de la carcinogenèse et de la régénération rénales – MUC1kid
The membrane-bound mucin MUC1 is expressed at the apical pole of epithelial cells and bears a long glycosylated extracellular domain (500 nm). MUC1 interacts with ErbB receptor family and plays a role in signal transduction. MUC1 contributes to tumour invasion by simultaneously disrupting existing interactions between opposing cells (anti-adhesion) and establishing new ligands for interaction between the invading cell and the adjoining cells (adhesion). Cancer cells may also use mucins to protect themselves from adverse cellular growth conditions and control the molecular microenvironment during invasion and metastasis. In Renal clear cell carcinoma (RCC), immunohistochemical studies have shown that MUC1 is frequently overexpressed. Its level of expression is correlated with Fuhrman grade and tumour progression and delocalization of its expression is associated with a worse prognosis. Clinical data suggest that MUC1 might be involved in renal tumour progression. In this project, we will test this hypothesis and evaluate the role of MUC1 on RCC by using in vitro and in vivo models. Recently, we have observed an epithelial-mesenchymal transition (EMT) concomitant to the overexpression of MUC1 in two human renal cell lines. EMT is an important mechanism during development, tissue regeneration and tumour progression (metastasis). To better understand the potential role of MUC1 during EMT, we will develop a murine model of renal regeneration. Our goals are (i) to decipher the role of MUC1 in renal tumour and regeneration, (ii) to identify new therapeutic targets and (iii) to propose new biological tools to the clinicians to ameliorate patient care.
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