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Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis

by Yu-Chin Liu 1,2, Chau-Ting Yeh 3 and Kwang-Huei Lin 1,2,3,4,*
1
Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan
2
Department of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan
3
Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
4
Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 4986; https://doi.org/10.3390/ijms20204986
Received: 31 August 2019 / Revised: 4 October 2019 / Accepted: 5 October 2019 / Published: 9 October 2019
(This article belongs to the Section Biochemistry)
Several physiological processes, including cellular growth, embryonic development, differentiation, metabolism and proliferation, are modulated by genomic and nongenomic actions of thyroid hormones (TH). Several intracellular and extracellular candidate proteins are regulated by THs. 3,3,5-Triiodo-L-thyronine (T3) can interact with nuclear thyroid hormone receptors (TR) to modulate transcriptional activities via thyroid hormone response elements (TRE) in the regulatory regions of target genes or bind receptor molecules showing no structural homology to TRs, such as the cell surface receptor site on integrin αvβ3. Additionally, L-thyroxine (T4) binding to integrin αvβ3 is reported to induce gene expression through initiating non-genomic actions, further influencing angiogenesis and cell proliferation. Notably, thyroid hormones not only regulate the physiological processes of normal cells but also stimulate cancer cell proliferation via dysregulation of molecular and signaling pathways. Clinical hypothyroidism is associated with delayed cancer growth. Conversely, hyperthyroidism is correlated with cancer prevalence in various tumor types, including breast, thyroid, lung, brain, liver and colorectal cancer. In specific types of cancer, both nuclear thyroid hormone receptor isoforms and those on the extracellular domain of integrin αvβ3 are high risk factors and considered potential therapeutic targets. In addition, thyroid hormone analogs showing substantial thyromimetic activity, including triiodothyroacetic acid (Triac), an acetic acid metabolite of T3, and tetraiodothyroacetic acid (Tetrac), a derivative of T4, have been shown to reduce risk of cancer progression, enhance therapeutic effects and suppress cancer recurrence. Here, we have reviewed recent studies focusing on the roles of THs and TRs in five cancer types and further discussed the potential therapeutic applications and underlying molecular mechanisms of THs. View Full-Text
Keywords: thyroid hormone; thyroid hormone receptor; 3,3,5-triiodo-L-thyronine (T3), L-thyroxine (T4), cancer proliferation thyroid hormone; thyroid hormone receptor; 3,3,5-triiodo-L-thyronine (T3), L-thyroxine (T4), cancer proliferation
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Liu, Y.-C.; Yeh, C.-T.; Lin, K.-H. Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis. Int. J. Mol. Sci. 2019, 20, 4986.

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