Integrin-Mediated Actions of Thyroid Hormone Analogues on Tumor Cell Chemosensitivity, Integrin-Growth Factor Receptor Crosstalk and Inflammatory Gene Expression


  •  Aleck H. Hercbergs    
  •  Faith B. Davis    
  •  Hung-Yun Lin    
  •  Mary K. Luidens    
  •  Ran Meng    
  •  Osnat Ashur-Fabian    
  •  Shaker A. Mousa    
  •  Paul J. Davis    

Abstract

Tetraiodothyroacetic acid (tetrac) and its nanoparticulate formulation induce apoptosis in cancer cells, oppose angiogenesis about xenografted human tumors and block cancer cell repair of double-stranded DNA breaks. These nongenomic actions of tetrac are initiated at a tetrac-thyroid hormone receptor on plasma membrane integrin avb3. In this review, we examine additional anti-cancer activities of tetrac formulations at avb3 and what is known about their mechanisms. These activities include 1) reversal of cancer cell chemoresistance (= induction of chemosensitization) and 2) disruption of crosstalk between avb3 and nearby cell surface growth factor receptors. In addition, nanoparticulate tetrac 3) alters expression of differentially-regulated inflammation-relevant genes that may be important to inflammation-supported cancer. For example, the agent downregulates genes whose products mediate cytokine responses and upregulates suppressor of cytokine signaling, SOCS4. Such actions of tetrac formulations define a multi-target functional profile, although the activities of tetrac begin at a single anatomic plasma membrane receptor on integrin avb3.



This work is licensed under a Creative Commons Attribution 4.0 License.
  • ISSN(Print): 1927-4858
  • ISSN(Online): 1927-4866
  • Started: 2012
  • Frequency: semiannual

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