The extracellular domain of plasma membrane integrin αvβ3 contains a cell 
surface receptor for thyroid hormone analogues. The receptor is largely 
expressed and activated in tumor cells and rapidly dividing endothelial cells. 
The principal ligand for this receptor is l-thyroxine (T4), usually regarded 
only as a prohormone for 3,5,3'-triiodo-l-thyronine (T3), the hormone analogue 
that expresses thyroid hormone in the cell nucleus via nuclear receptors that 
are unrelated structurally to integrin αvβ3. At the integrin receptor for 
thyroid hormone, T4 regulates cancer and endothelial cell division, tumor cell 
defense pathways (such as anti-apoptosis), and angiogenesis and supports 
metastasis, radioresistance, and chemoresistance. The molecular mechanisms 
involve signal transduction via mitogen-activated protein kinase and 
phosphatidylinositol 3-kinase, differential expression of multiple genes related 
to the listed cell processes, and regulation of activities of other cell surface 
proteins, such as vascular growth factor receptors. Tetraiodothyroacetic acid 
(tetrac) is derived from T4 and competes with binding of T4 to the integrin. In 
the absence of T4, tetrac and chemically modified tetrac also have anticancer 
effects that culminate in altered gene transcription. Tumor xenografts are 
arrested by unmodified and chemically modified tetrac. The receptor requires 
further characterization in terms of contributions to nonmalignant cells, such 
as platelets and phagocytes. The integrin αvβ3 receptor for thyroid hormone 
offers a large panel of cellular actions that are relevant to cancer biology and 
that may be regulated by tetrac derivatives.