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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adenoma, Animals, Caco-2 Cells, Cadherins, Carcinoma, Cell Differentiation, Cell Proliferation, Colon, Colonic Neoplasms, Female, Gene Expression Regulation, HCT116 Cells, Humans, Iodide Peroxidase, Mice, Mice, Inbred BALB C, Mice, Nude, Plasmids, RNA, Messenger, Transcription Factor 7-Like 2 Protein, Transfection, Transplantation, Heterologous, Triiodothyronine, Wnt Signaling Pathway, beta Catenin.
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Does β-Catenin regulate deiodinase levels and thyroid hormone signaling in colon cancer cells? Context: Activation of the β-catenin/T-cell factor (TCF) complex occurs in most colon tumors, and its actions correlate with the neoplastic phenotype of intestinal epithelial cells. Type 3 deiodinase (D3), the selenoenzyme that inactivates thyroid hormone (3,5,3' triiodothyronine [T3]), is frequently expressed by tumor cells, but little is known about its role in the regulation of T3 signaling in cancer cells. We measured D3 expression in 6 colon cancer cell lines and human tumors and correlated it with the activity of the β-catenin/TCF complex. We also determined the effects of D3 loss on local thyroid hormone signaling and colon tumorigenesis. We show that D3 is a direct transcriptional target of the β-catenin/TCF complex; its expression was higher in human intestinal adenomas and carcinomas than in healthy intestinal tissue. Experimental attenuation of β-catenin reduced D3 levels and induced type 2 deiodinase (the D3 antagonist that converts 3,5,3',5' tetraiodothyronine into active T3) thereby increasing T3-dependent transcription. In the absence of D3, excess T3 reduced cell proliferation and promoted differentiation in cultured cells and in xenograft mouse models. This occurred via induction of E-cadherin, which sequestered β-catenin at the plasma membrane and promoted cell differentiation.
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Deiodinases are at the interface between the β-catenin and the thyroid hormone pathways. Their synchronized regulation of intracellular T3 concentration is a hitherto unrecognized route by which the multiple effects of β-catenin are generated and may be targeted to reduce the oncogenic effects of β-catenin in intestinal cells. Final Decision: yes