Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor

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In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
04:14

In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse

Published on: October 6, 2023

Paul J Davis1, Faith B Davis, Hung-Yun Lin

  • 1Signal Transduction Laboratory, Ordway Research Institute, Albany, NY 12208, USA. pdavis@ordwayresearch.org

American Journal of Physiology. Endocrinology and Metabolism
|September 17, 2009
PubMed

Insights

Thyroid hormone actions at the cell surface, mediated by integrin alphavbeta3, influence tumor cell proliferation and angiogenesis via ERK1/2 and PI3K pathways. Tetraiodothyroacetic acid (tetrac) acts as an inhibitor and probe for these nongenomic mechanisms.

Area of Science:

  • Molecular Endocrinology
  • Cancer Biology
  • Cell Signaling

Background:

  • Thyroid hormones (T4 and T3) exert nongenomic effects initiated at the cell surface via integrin alphavbeta3.
  • These nongenomic actions regulate tumor cell proliferation and angiogenesis.
  • Signal transduction involves extracellular-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K) pathways.

Discussion:

  • Integrin-initiated thyroid hormone signaling impacts tumor cell division (ERK1/2) and angiogenesis (PI3K).
  • Tetraiodothyroacetic acid (tetrac) inhibits and probes these cell surface-initiated actions.
  • Tetrac also exhibits independent effects on gene transcription in tumor cells.

Key Insights:

  • A cell surface receptor on integrin alphavbeta3 mediates rapid, nongenomic thyroid hormone effects.
  • Distinct signaling pathways (ERK1/2, PI3K) are involved in different cellular responses.
  • Tetrac serves as a crucial tool for investigating these mechanisms and their therapeutic potential.

Outlook:

  • Translating these nongenomic mechanisms into clinical cancer therapy is a promising avenue.
  • Targeting integrin-mediated thyroid hormone signaling could offer novel anti-cancer strategies.
  • Further research is needed to fully elucidate the clinical implications for cancer and non-cancer angiogenesis.

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