Novel non-genomic signaling of thyroid hormone receptors in thyroid carcinogenesis
Guigon CJ et al. – Review article highlights the recent advances in understanding of the critical role of novel non-genomic actions of mutations of thyroid hormone receptor (TR) in thyroid carcinogenesis.- Studies so far have shown that the deleterious effects of TRβ mutants in causing resistance to thyroid hormone (RTH) are mediated via dominant negative actions at the transcriptional level
- However, novel modes of TRβ mutant actions have been identified from mice study that are beyond nucleus-initiated transcription:
- Direct protein–protein interaction with the PI3K leads to cell proliferation, apoptosis, migration, and metastasis
- Direct interation with PTTG or β-catenin affects their degradation by the proteasomal pathways, thus leading to PTTG and β-catenin aberrant accumulation
- This contributes to genetic instability and constitutively active β-catenin oncogenic signaling to affect cell proliferation and migration
- Therefore, the development and progression of thyroid tumors in mice not only involve impaired transcriptional activity but also derailed post-transcriptional mechanisms
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