Radioresistance of cancer cells, integrin αvβ3 and thyroid hormone

John T. Leith, Shaker A. Mousa, Aleck Hercbergs, Hung-Yun Lin and Paul J. Davis _

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Oncotarget. 2018; 9:37069-37075. https://doi.org/10.18632/oncotarget.26434

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John T. Leith1, Shaker A. Mousa2, Aleck Hercbergs3, Hung-Yun Lin4,5,6,7 and Paul J. Davis2,8

1Rhode Island Nuclear Science Center, Narragansett, RI, USA

2Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA

3Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA

4Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan

5PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

6Traditional Herbal Medicine Research Center, Taipei Medical University, Taipei, Taiwan

7TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan

8Department of Medicine, Albany Medical College, Albany, NY, USA

Correspondence to:

Paul J. Davis, email: [email protected]

Keywords: integrin open configuration; AKT; epithelial-mesenchymal transition (EMT); L-thyroxine (T4); STAT3

Received: August 30, 2018     Accepted: November 16, 2018     Published: December 11, 2018


Radioresistance is a substantial barrier to success in cancer management. A number of molecular mechanisms support radioresistance. We have shown experimentally that the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3 may modulate the state of radiosensitivity of tumor cells. Specifically, tetraiodothyroacetic acid (tetrac), a derivative of L-thyroxine (T4), can reduce radioresistance in cancer cells. In this review, we list a number of intrinsic signal transduction molecules and other host factors that have been reported to support/induce radioresistance in cancer cells and that are also subject to control by T4 through actions primarily initiated at integrin αvβ3. Additional preclinical evidence is needed to support these radioresistance-relevant actions of thyroid hormone.

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