Review articleThe thyroid hormone nuclear receptors and the Wnt/β-catenin pathway: An intriguing liaison

- The TRs are involved in developmental and homeostatic processes.
- They display multilevel interactions with the Wnt canonical pathway.
- These interactions occur both under physiological and pathological conditions.
- The complex crosstalk between TRs and the Wnt pathway involves tissue-specific stem cells.

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.