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Rôle de la cadhérine atypique MUCDHL dans le système digestif et ses pathologies

Abstract : MUCDHL is an atypical cadherin that has been poorly studied. The data obtained so far suggest that this gene has tumor suppressive activity in the intestine, namely by its interaction and inhibitory effect on β-catenin, and that its expression is frequently decreased in colorectal cancers (CCR). In parallel to this anti-oncogenic function, other studies have suggested that MUCDHL is involved in the assembly of the intestinal brush border (BB), by contributing to the formation of an inter-microvilli interaction complex. Our objective was to determine the function and mode of action of MUCDHL in the digestive system, Through a detailed characterization of the interaction with β-catenin, we showed that the anti-oncogenic mode of action of MUCDHL is more complex than a simple membrane sequestration of β-catenin. In addition, we confirmed the tumor suppressive function of MUCDHL on a very large cohort of human CCR and showed for the first time that its loss amplifies intestinal tumorigenesis in a murine model. Moreover, the study of the phenotype of Mucdhl-/- mice allowed us to demonstrate the importance of MUCDHL in the homeostasis of the digestive system. Indeed, the absence of MUCDHL causes morphological alterations of the intestinal BB, but also numerous metabolic disturbances. Thus, this work provides new information on the function and mode of action of MUCDHL in the digestive system.
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Submitted on : Friday, February 1, 2019 - 12:16:36 PM
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Ahlam Moufok-Sadoun. Rôle de la cadhérine atypique MUCDHL dans le système digestif et ses pathologies. Cancer. Université de Strasbourg, 2017. Français. ⟨NNT : 2017STRAJ075⟩. ⟨tel-02003540⟩

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