Contributions of thyroid hormone to cancer metastasis

Shaker A. Mousa, Gennadi V. Glinsky, Hung Yun Lin, Osnat Ashur-Fabian, Aleck Hercbergs, Kelly A. Keating, Paul J. Davis

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)

Abstract

Acting at a cell surface receptor on the extracellular domain of integrin αvβ3, thyroid hormone analogues regulate downstream the expression of a large panel of genes relevant to cancer cell proliferation, to cancer cell survival pathways, and to tumor-linked angiogenesis. Because αvβ is involved in the cancer cell metastatic process, we examine here the possibility that thyroid hormone as L-thyroxine (T4) and the thyroid hormone antagonist, tetraiodothyroacetic acid (tetrac), may respectively promote and inhibit metastasis. Actions of T4 and tetrac that are relevant to cancer metastasis include the multitude of synergistic effects on molecular levels such as expression of matrix metalloproteinase genes, angiogenesis support genes, receptor tyrosine kinase (EGFR/ERBB2) genes, specific microRNAs, the epithelial-mesenchymal transition (EMT) process; and on the cellular level are exemplified by effects on macrophages. We conclude that the thyroid hormone-αvβ interaction is mechanistically linked to cancer metastasis and that modified tetrac molecules have antimetastatic activity with feasible therapeutic potential.

Original languageEnglish
Article number89
JournalBiomedicines
Volume6
Issue number3
DOIs
Publication statusPublished - Sep 1 2018

Keywords

  • Angiogenesis
  • Cancer
  • Cancer cell genes
  • Epithelial-to-mesenchymal transition (EMT)
  • Integrin αvβ3
  • L-thyroxine
  • Matrix metalloproteinases
  • Metastasis
  • T4
  • Tetrac
  • Thyroid hormone

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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