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Étude du signal véhiculé par les hormones thyroïdiennes dans la physiopathologie intestinale

Abstract : The intestinal epithelium is characterized by constant renewal and differentiation due to the presence of stem cells located at the bottom of the crypts. This permanent renewal depends on the crosstalk between several signaling pathways whose alteration can lead to tumor initiation and progression. Our team demonstrated the implication of the thyroid hormones and their nuclear receptor TRa1 in the control of the intestinal epithelium homeostasis through the regulation of the Wnt pathway. Moreover, the overexpression of TRa1 in the intestinal epithelium of mice is sufficient to promote tumor initiation, and in an APC loss of function context, it accelerates tumor progression highlighting its oncogenic potential. Through gene expression profiling, we highlighted an activation of the Wnt pathway activity by TRa1 during tumor progression. We next confirm these results in human patient samples by demonstrating that high TRa1 expression in tumors invariably is associated with an increased Wnt pathway activity. In addition, in CRC cell lines, TRa1-associated WNT pathway activation enhances their aggressiveness. Altogether these results showed the implication of TRa1 in intestinal carcinogenesis and open avenues for new therapeutic treatment against TRa1 targeting TRa1
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Luis Joël Uchuya Castillo. Étude du signal véhiculé par les hormones thyroïdiennes dans la physiopathologie intestinale. Biologie cellulaire. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1221⟩. ⟨tel-01743821⟩

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