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Cited by 34Thyroid Disorders and TreatmentsEstrogen and related hormone effectsThyroid Cancer Diagnosis and Treatment

Bioactivity of thyroid hormone analogs at cancer cells

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Davis, Paul J., Tang, Heng-Yuan, Hercbergs, Aleck, Lin, Hung-Yun, Keating, Kelly A., Mousa, Shaker A.·2018·Frontiers in Endocrinology
DOI 10.3389/fendo.2018.00739PMC PMC6288194
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Abstract

In the context of genomic thyroid hormone actions in normal (noncancer) cells that involve primary interactions with nuclear thyroid hormone receptors (TRs), L-thyroxine (T4), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) have little bioactivity. In terms of TRs, T4 is a prohormone from which the active nuclear ligand, 3,5,3'-triido-L-thyronine (T3), is generated by deiodination. Deaminated T4 and T3 metabolites have different genomic effects: tetraiodothyroacetic acid (tetrac) is a low grade thyromimetic derivative of T4, whereas triiodothyroacetic acid (triac), the acetic acid metabolite of T3, has substantial thyromimetic activity. In cancer cells, the cell surface receptor for thyroid hormone on integrin αvβ3 mediates non-genomic actions of thyroid hormone analogs. The integrin is expressed in large measure by cancer cells and dividing endothelial cells and has a substantially different panel of responses to thyroid hormone analogs. At αvβ3, T4 is a potent proliferative, anti-apoptotic and pro-angiogenic hormone and is the primary ligand. rT3 may also be proliferative at this site. In contrast, tetrac and triac are antagonists of T4 at αvβ3, but also have anticancer properties at this site that are independent of their effects on the binding of T4.

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  • T4 also binds to cell membrane-located ανβ3 integrin receptors which exert rapid signaling via various kinase and intracellular pathways, especially in tumor cells and stem cells.

    “Over the last years, some evidence has been presented that T4 also binds to cell membrane-located ανβ3 integrin receptors which exert rapid signaling via various kinase and intracellular pathways, especially in tumor cells and stem cells (7, 8).”

    From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [7]

    The Introduction identifies a cell-surface thyroid-hormone receptor on integrin αvβ3, and “Bioactivity of T4 at αvβ3” describes T4-mediated MAPK/ERK1/2 and PI3K signaling relevant to cancer cells. The cited passages discuss cancer cells and rapidly dividing endothelial cells, but do not establish the claim’s specific emphasis on stem cells; a search for “stem cells” found no supporting passage. No page numbers are available in our copy. (LLM, conf=0.87)

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Research works printed but not linked: 38

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Cited by

Sorted by citations

Authors
Davis, P. J., Tang, H.-Y., Hercbergs, A., Lin, H.-Y., Keating, K. A., & Mousa, S. A.
Affiliations
  • Albany College of Pharmacy and Health Sciences (US)
  • Cleveland Clinic (US)
  • Taipei Medical University Hospital (TW)
Corresponding author
Davis, Paul J.
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2018-12-04
Volume
9
Pages
739-739
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2018.00739
PMC
PMC6288194
OpenAlex
W2902018992
Cited by
34
References
0
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 2
FWCI
0.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Rensselaer Polytechnic Institute
  • Ministry of Education, India
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords
thyroid hormone analogs, thyroid hormone receptor, levothyroxine, reverse T3, tetraiodothyroacetic acid, triiodothyroacetic acid, integrin αvβ3, tumor cell proliferation, anti-apoptotic effects, angiogenesis, anticancer activity, deiodination

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