ArticleEndocrinology2014
The sonic hedgehog-induced type 3 deiodinase facilitates tumorigenesis of basal cell carcinoma by reducing Gli2 inactivation.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Genetics of selenoproteins and selenoprotein metabolism - An overview of current concepts and emerging aspects.Redox biology · 2026Review
- The thyroid hormone activating enzyme, DIO2, is a potential pan-cancer biomarker and immunotherapy target.Journal of endocrinological investigation · 2025Article
- Type 2 deiodinase is expressed in anaplastic thyroid carcinoma and its inhibition causes cell senescence.Endocrine-related cancer · 2023Article
- The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas.Cancers · 2022Review
- µ-Crystallin Is Associated with Disease Outcome in Head and Neck Squamous Cell Carcinoma.Journal of personalized medicine · 2021Article
- Deiodinases and Cancer.Endocrinology · 2021Review
- Sonic Hedgehog and Triiodothyronine Pathway Interact in Mouse Embryonic Neural Stem Cells.International journal of molecular sciences · 2020Article
- Article
- Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch.Nature communications · 2019Article
- Deiodinases and their intricate role in thyroid hormone homeostasis.Nature reviews. Endocrinology · 2019Review
- The Role of Thyroid Hormones in Hepatocyte Proliferation and Liver Cancer.Frontiers in endocrinology · 2019Review
- Thyroid Hormones and Cancer: A Comprehensive Review of Preclinical and Clinical Studies.Frontiers in endocrinology · 2019Review
- Deiodinases and stem cells: an intimate relationship.Journal of endocrinological investigation · 2018Review
- Article
- Reciprocal interplay between thyroid hormone and microRNA-21 regulates hedgehog pathway-driven skin tumorigenesis.The Journal of clinical investigation · 2016Article
- A novel tumor suppressor gene in basal cell carcinoma: inhibition of growth factor-2.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Type 3 deiodinase: role in cancer growth, stemness, and metabolism.Frontiers in endocrinology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Thyroid hormone (TH) is an important regulator of growth, development, and metabolism. Most of the active TH T3 is generated by peripheral TH metabolism mediated by the iodothyronine deiodinases. Type 3 deiodinase (D3) inactivates T3 via specific deiodination reactions. It is an oncofetal protein frequently expressed in neoplastic tissues and is a direct target of the sonic hedgehog (Shh) pathway in basal cell carcinomas (BCCs). However, the molecular mechanisms triggered by T3 in BCC are still mostly unrevealed. Here, we demonstrate that D3 action is critical in the proliferation and survival of BCC cells. D3 depletion or T3 treatment induce apoptosis of BCC cells and attenuate Shh signaling. This is achieved through a direct impairment of Gli2 protein stability by T3. T3 induces protein kinase A, which in turn destabilizes Gli2 protein via its C-terminal degron. Finally, in a mouse model of BCC, T3-topical treatment significantly reduces tumor growth. These results demonstrate the existence of a previously unrecognized cross talk between TH and Gli2 oncogene, providing functional and mechanistic evidence of the involvement of TH metabolism in Shh-induced cancer. TH-mediated Gli2 inactivation would be beneficial for therapeutically purposes, because the inhibition of Shh-Gli2 signaling is an attractive target for several anticancer drugs, currently in clinical trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.