Abstract
A pivotal role of thyroid hormones and their nuclear receptors in intestinal development and homeostasis have been described, whereas their involvement in intestinal carcinogenesis is still controversial. In this perspective article we briefly summarize the recent advances in this field and present new data regarding their functional interaction with one of the most important signaling pathway, such as WNT, regulating intestinal development and carcinogenesis. These complex interactions unveil new concepts and will surely be of importance for translational research.
Highlights
The role of the Thyroid Hormones (THs) in intestinal development have been established since the beginning of the 20th century based on the observations on amphibian metamorphosis
When TRa1 is up-regulated in a normal context it stimulates its target genes including bcatenin, resulting in the activation of the WNT pathway and, by consequence, increased crypt proliferation, through the mechanisms we have already described [41, 48]
We may speculate that the “displacement” of TRa1 can be considered the molecular counterpart of the WNT hyperactivation resulting from the interaction of this two signalling pathways
Summary
The role of the Thyroid Hormones (THs) in intestinal development have been established since the beginning of the 20th century based on the observations on amphibian metamorphosis. To analyze the specific DNA binding of b-catenin/ Tcf on their target genes and the eventual presence of TRa1 in the same regions, we decided to look at WREs described within the Axin2 [44] and c-Myc [45], two classical direct WNT targets In both cases (Figure 1D) TRa1 was not present on the WRE regions in the WT intestine but was clearly enriched on them, both in normal mucosae and the tumors of vil-TRa1/Apc mice (Figure 1D). In vil-TRa1/Apc mice, the stronger b-catenin stabilization and Tcf overexpression might induce a competitive shift in TRa1 binding from TREs to WREs. We can speculate that this mechanism is one of the factors responsible for the activation and/or the acceleration of the tumorigenic process dependent upon TRa1-up regulation. Amplify the transcriptional response dependent upon the WNT effectors b-catenin/Tcf
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
