Submitted on August 5, 2009
Revised on September 8, 2009
Accepted on September 13, 2009
Translational Implications of Nongenomic Actions of Thyroid Hormone Initiated at its Integrin Receptor
Paul J. Davis1, Faith B. Davis2*, Hung-Yun Lin2, Shaker A. Mousa3, Min Zhou2, and Mary K. Luidens1
1 Albany Medical College
2 Ordway Research Institute
3 Albany College of Pharmacy
* To whom correspondence should be addressed. E-mail: fdavis{at}ordwayresearch.org.
A thyroid hormone receptor on integrin 
v
3 has been described that mediates cell surface-initiated, nongenomic actions of thyroid hormone on tumor cell proliferation and on angiogenesis. Transduction of the hormone signal into these recently-recognized proliferative effects is by extracellular regulated kinases 1/2 (ERK1/2). Other nongenomic actions of the hormone may be transduced by phosphatidylinositol 3-kinase (PI 3-K) and are initiated in cytoplasm or at the cell surface. PI 3-K-mediated effects are important to angiogenesis or other recently-appreciated cell functions, but apparently not to tumor cell division. For those actions of thyroid hormone (L-thyroxine, T4, and 3, 5, 3'-triiodo-L-thyronine, T3) that begin at the integrin receptor, tetraiodothyroacetic acid (tetrac) is an inhibitor of and probe for the participation of the receptor in downstream intracellular events. In addition, tetrac has actions initiated at the integrin receptor that are unrelated to inhibition of the effects of T4 and T3 and that involve gene transcription in tumor cells. Discussed here are the implications of translating these nongenomic mechanisms of thyroid hormone analogues into clinical cancer cell biology, tumor-related angiogenesis and modulation of angiogenesis that is not related to cancer.
