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The thyroid hormone nuclear receptors and the Wnt/β-catenin pathway: An intriguing liaison
Seham Skah1, Joel Uchuya-Castillo1, Maria Sirakov1
1Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR5286, Université de Lyon, Université Lyon 1, Centre Léon Bérard, Département de la recherche, 69373 Lyon, France.
Abstract:
The thyroid hormones, T3 and T4, control several developmental and homeostatic processes. From a molecular point of view, most of their actions depend on the activity of the thyroid hormone nuclear receptors (TRs), which are T3-modulated transcription factors. Recent studies have not only highlighted that the physiological response induced by T3 within a cell depends on the expression of specific TRs, but also that the functions of TRs are coordinated by and integrated in other signalling pathways. This is particularly the case for the multilevel interactions between TRs and the Wnt signalling pathway. Interestingly both signals are involved in development and homeostasis, and their alterations are responsible for the development of pathologies, such as cancer. Here, we present findings on the complex crosstalk between TRs and Wnt in several organisms and in different tissue contexts, and speculate on the biological relevance of modulating TR-Wnt functionality in therapeutic approaches aimed to target cancer cells or applications for regenerative medicine.
Insights
Thyroid hormones (T3 and T4) and Wnt signaling interact intricately. Understanding this crosstalk is key for developing new cancer therapies and regenerative medicine strategies.
Area of Science:
- Molecular Biology
- Endocrinology
- Developmental Biology
Background:
- Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), regulate vital physiological processes.
- Thyroid hormone nuclear receptors (TRs) mediate most thyroid hormone actions by modulating gene transcription.
- TRs function is influenced by other signaling pathways, notably the Wnt pathway.
Purpose of the Study:
- To explore the complex interplay between TRs and the Wnt signaling pathway.
- To investigate the role of this crosstalk in development, homeostasis, and disease.
- To evaluate the therapeutic potential of modulating TR-Wnt interactions.
Main Methods:
- Review of existing literature on TRs and Wnt signaling.
- Analysis of findings across various organisms and tissue types.
- Speculative analysis of biological relevance and therapeutic applications.
Main Results:
- TRs and Wnt signaling exhibit multilevel interactions.
- Both pathways are crucial for development and homeostasis.
- Dysregulation of these pathways is linked to pathologies like cancer.
Conclusions:
- The crosstalk between TRs and Wnt signaling is complex and significant.
- Modulating TR-Wnt functionality offers potential therapeutic avenues for cancer and regenerative medicine.
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