Membrane receptor for thyroid hormone: physiologic and pharmacologic implications.

Plasma membrane integrin αvβ3 is a cell surface receptor for thyroid hormone at which nongenomic actions are initiated. L-thyroxine (T₄) and 3,3',5-triiodo-L-thyronine (T₃) promote angiogenesis and tumor cell proliferation via the receptor. Tetraiodothyroacetic acid (tetrac), a deaminated T₄ derivative, blocks the nongenomic proliferative and proangiogenic actions of T₄ and T₃. Acting at the integrin independently of T₄ and T₃, tetrac and a novel nanoparticulate formulation of tetrac that acts exclusively at the cell surface have oncologically desirable antiproliferative actions on multiple tumor cell survival pathway genes. These agents also block the angiogenic activity of vascular growth factors. Volume and vascular support of xenografts of human pancreatic, kidney, lung, and breast cancers are downregulated by tetrac formulations. The integrin αvβ3 receptor site for thyroid hormone selectively regulates signal transduction pathways and distinguishes between unmodified tetrac and the nanoparticulate formulation. The receptor also mediates nongenomic thyroid hormone effects on plasma membrane ion transporters and on intracellular protein trafficking.

[1]  F. B. Davis,et al.  Human Platelet Aggregation and Degranulation Is Induced In Vitro by L-Thyroxine, but Not by 3,5,3′-Triiodo-L-Thyronine or Diiodothyropropionic Acid (DITPA) , 2010, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[2]  Herng‐Ching Lin,et al.  Hyperthyroidism and Risk of Ischemic Stroke in Young Adults: A 5-Year Follow-Up Study , 2010, Stroke.

[3]  F. B. Davis,et al.  Tetraiodothyroacetic acid (tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid. , 2010, The Journal of clinical endocrinology and metabolism.

[4]  P. Davis,et al.  Molecular aspects of thyroid hormone actions. , 2010, Endocrine reviews.

[5]  Emmy Dier,et al.  Tetraiodothyroacetic acid and tetraiodothyroacetic acid nanoparticle effectively inhibit the growth of human follicular thyroid cell carcinoma. , 2010, Thyroid : official journal of the American Thyroid Association.

[6]  F. B. Davis,et al.  Mini-review: Cell surface receptor for thyroid hormone and nongenomic regulation of ion fluxes in excitable cells , 2010, Physiology & Behavior.

[7]  B. Vincenzi,et al.  Cetuximab: from bench to bedside. , 2010, Current cancer drug targets.

[8]  J. Norman,et al.  Integrins: masters and slaves of endocytic transport , 2009, Nature Reviews Molecular Cell Biology.

[9]  Min Zhou,et al.  Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor. , 2009, American journal of physiology. Endocrinology and metabolism.

[10]  F. B. Davis,et al.  Effects of Resin or Charcoal Treatment on Fetal Bovine Serum and Bovine Calf Serum , 2009, Endocrine research.

[11]  H. Modjtahedi,et al.  Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opportunities. , 2009, Anti-cancer drugs.

[12]  F. B. Davis,et al.  Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac) , 2009, Cell cycle.

[13]  F. B. Davis,et al.  Tetraidothyroacetic acid (tetrac) and tetrac nanoparticles inhibit growth of human renal cell carcinoma xenografts. , 2009, Anticancer research.

[14]  F. B. Davis,et al.  Radiosensitization of GL261 glioma cells by tetraiodothyroacetic acid (tetrac) , 2009, Cell cycle.

[15]  P. Billings,et al.  The structure and function of platelet integrins , 2009, Journal of thrombosis and haemostasis : JTH.

[16]  F. B. Davis,et al.  The pro-apoptotic action of stilbene-induced COX-2 in cancer cells: Convergence with the anti-apoptotic effect of thyroid hormone , 2009, Cell cycle.

[17]  A. Ribera,et al.  Molecular components underlying nongenomic thyroid hormone signaling in embryonic zebrafish neurons , 2009, Neural Development.

[18]  F. B. Davis,et al.  L-Thyroxine vs. 3,5,3'-triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. , 2009, American journal of physiology. Cell physiology.

[19]  T. Byzova,et al.  Cooperation between integrin ανβ3 and VEGFR2 in angiogenesis , 2009, Angiogenesis.

[20]  F. B. Davis,et al.  Cytoplasm-To-Nucleus Shuttling Of Thyroid Hormone Receptor-β1 (Trβ1) Is Directed From A Plasma Membrane Integrin Receptor By Thyroid Hormone , 2009, Endocrine research.

[21]  Jianxiang Wang,et al.  Down-regulation of P-glycoprotein expression by sustained intracellular acidification in K562/Dox cells. , 2008, Biochemical and biophysical research communications.

[22]  A. Ribera,et al.  Sensory neuron sodium current requires nongenomic actions of thyroid hormone during development. , 2008, Journal of neurophysiology.

[23]  E. Cohen-Jonathan-Moyal,et al.  αvβ3 and αvβ5 integrins control glioma cell response to ionising radiation through ILK and RhoB , 2008, International journal of cancer.

[24]  F. B. Davis,et al.  Mechanisms of nongenomic actions of thyroid hormone , 2008, Frontiers in Neuroendocrinology.

[25]  F. B. Davis,et al.  Novel function of the thyroid hormone analog tetraiodothyroacetic acid: a cancer chemosensitizing and anti-cancer agent , 2008, Angiogenesis.

[26]  Jianxun Lei,et al.  T3 increases Na-K-ATPase activity via a MAPK/ERK1/2-dependent pathway in rat adult alveolar epithelial cells. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[27]  S. Vukicevic,et al.  Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss , 2008, Proceedings of the National Academy of Sciences.

[28]  M. Parsons,et al.  Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin alphaVbeta3. , 2008, The Journal of endocrinology.

[29]  Elena Silvestri,et al.  Metabolic effects of thyroid hormone derivatives. , 2008, Thyroid : official journal of the American Thyroid Association.

[30]  A. Bianco,et al.  Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. , 2008, Endocrine reviews.

[31]  V. Mehta,et al.  HB-EGF stimulates eNOS expression and nitric oxide production and promotes eNOS dependent angiogenesis , 2008, Growth factors.

[32]  J. Pedersen,et al.  Involvement of plasma membrane redox systems in hormone action , 2007, The Journal of pharmacy and pharmacology.

[33]  S. Rodan,et al.  Involvement of αvβ3 integrins in osteoclast function , 2007, Journal of Bone and Mineral Metabolism.

[34]  F. B. Davis,et al.  Molecular modeling of the thyroid hormone interactions with αvβ3 integrin , 2007, Steroids.

[35]  Hung-Yun Lin,et al.  Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic , 2007, Steroids.

[36]  Thomas S. Scanlan,et al.  Rapid nongenomic actions of thyroid hormone , 2006, Proceedings of the National Academy of Sciences.

[37]  Alexandra M. Dumitrescu,et al.  Thyroid hormone mediated changes in gene expression can be initiated by cytosolic action of the thyroid hormone receptor β through the phosphatidylinositol 3-kinase pathway , 2006, Nuclear receptor signaling.

[38]  F. B. Davis,et al.  Proangiogenesis action of the thyroid hormone analog 3,5-diiodothyropropionic acid (DITPA) is initiated at the cell surface and is integrin mediated. , 2006, Endocrinology.

[39]  P. Yen,et al.  Thyroid hormone action at the cellular, genomic and target gene levels , 2006, Molecular and Cellular Endocrinology.

[40]  J. Chu,et al.  Quantifying the Specific Binding between West Nile Virus Envelope Domain III Protein and the Cellular Receptor αVβ3 Integrin* , 2006, Journal of Biological Chemistry.

[41]  J. Norman,et al.  Integrin Trafficking and the Control of Cell Migration , 2006, Traffic.

[42]  F. B. Davis,et al.  Membrane receptors mediating thyroid hormone action , 2005, Trends in Endocrinology & Metabolism.

[43]  M. Holick,et al.  Topical thyroid hormone accelerates wound healing in mice. , 2005, Endocrinology.

[44]  F. B. Davis,et al.  The Proangiogenic Action of Thyroid Hormone Analogue GC-1 Is Initiated at an Integrin , 2005, Journal of cardiovascular pharmacology.

[45]  F. B. Davis,et al.  Rapid nongenomic effects of 3,5,3'-triiodo-L-thyronine on the intracellular pH of L-6 myoblasts are mediated by intracellular calcium mobilization and kinase pathways. , 2004, Endocrinology.

[46]  F. B. Davis,et al.  Thyroid hormone causes mitogen-activated protein kinase-dependent phosphorylation of the nuclear estrogen receptor. , 2004, Endocrinology.

[47]  Hung-Yun Lin,et al.  Proangiogenic Action of Thyroid Hormone Is Fibroblast Growth Factor–Dependent and Is Initiated at the Cell Surface , 2004, Circulation research.

[48]  M. Holick,et al.  A role for thyroid hormone in wound healing through keratin gene expression. , 2004, Endocrinology.

[49]  Hung-Yun Lin,et al.  Disparate effects of thyroid hormone on actions of epidermal growth factor and transforming growth factor-alpha are mediated by 3',5'-cyclic adenosine 5'-monophosphate-dependent protein kinase II. , 2004, Endocrinology.

[50]  F. B. Davis,et al.  Identification of the putative MAP kinase docking site in the thyroid hormone receptor-beta1 DNA-binding domain: functional consequences of mutations at the docking site. , 2003, Biochemistry.

[51]  M. Lark,et al.  Rapid inhibition of thyroxine-induced bone resorption in the rat by an orally active vitronectin receptor antagonist. , 2002, The Journal of pharmacology and experimental therapeutics.

[52]  G. Hager,et al.  Nuclear Cytoplasmic Shuttling by Thyroid Hormone Receptors , 2001, The Journal of Biological Chemistry.

[53]  F. B. Davis,et al.  Thyroid hormone promotes serine phosphorylation of p53 by mitogen-activated protein kinase. , 2001, Biochemistry.

[54]  Hung-Yun Lin,et al.  Thyroxine Promotes Association of Mitogen-activated Protein Kinase and Nuclear Thyroid Hormone Receptor (TR) and Causes Serine Phosphorylation of TR* , 2000, The Journal of Biological Chemistry.

[55]  Li Zhang,et al.  Ligand Binding to Integrins* , 2000, The Journal of Biological Chemistry.

[56]  Y. Chen,et al.  Thyroid hormone, T3-dependent phosphorylation and translocation of Trip230 from the Golgi complex to the nucleus. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[57]  S. Cheng,et al.  Hormone-induced Translocation of Thyroid Hormone Receptors in Living Cells Visualized Using a Receptor Green Fluorescent Protein Chimera* , 1998, The Journal of Biological Chemistry.

[58]  F. B. Davis,et al.  Potentiation by Thyroid Hormone of Human IFN-γ-Induced HLA-DR Expression , 1998, The Journal of Immunology.

[59]  P. Campochiaro,et al.  Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[60]  F. B. Davis,et al.  Thyroid hormone analogues potentiate the antiviral action of interferon‐γ by two mechanisms , 1996 .

[61]  J. L. Leonard,et al.  Thyroxine-dependent regulation of integrin-laminin interactions in astrocytes. , 1995, Endocrinology.

[62]  F. Faas,et al.  Effect of a protein-free diet on muscle protein turnover and nitrogen conservation in euthyroid and hyperthyroid rats. , 1984, The Biochemical journal.

[63]  H. Coley.  Overcoming multidrug resistance in cancer: clinical studies of p-glycoprotein inhibitors. , 2010, Methods in molecular biology.

[64]  Michael A Vogelbaum,et al.  Future of convection-enhanced delivery in the treatment of brain tumors. , 2010, Future oncology.

[65]  U. Reuning,et al.  Integrin alphavbeta3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells. , 2008, The international journal of biochemistry & cell biology.

[66]  Shaker A. Mousa,et al.  Tetraiodothyroacetic acid, a small molecule integrin ligand, blocks angiogenesis induced by vascular endothelial growth factor and basic fibroblast growth factor , 2007, Angiogenesis.

[67]  S. J. Stachelek,et al.  Regulation of cerebellar neuronal migration and neurite outgrowth by thyroxine and 3,3',5'-triiodothyronine. , 2005, Brain research. Developmental brain research.

[68]  S. Incerpi,et al.  Short-term effects of thyroid hormones on the Na/H antiport in L-6 myoblasts: high molecular specificity for 3,3',5-triiodo-L-thyronine. , 1999, Endocrinology.

[69]  Integrin (cid:1) V (cid:2) 3 Contains a Cell Surface Receptor Site for Thyroid Hormone that Is Linked to Activation of Mitogen-Activated Protein Kinase and Induction of Angiogenesis , 2022 .