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Thyroid hormone, PD-L1, and cancer
Yi-Ru Chen1, Zi-Lin Li1, Ya-Jung Shih1, Paul J Davis2, Jaqueline Whang-Peng3, Hung-Yun Lin4, Kuan Wang1
1 Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
2 The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer; Department of Medicine, Albany Medical College, Albany, NY, USA
3 Taipei Cancer Center; Cancer Center, Wan Fang Hospital; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
4 Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA; Cancer Center, Wan Fang Hospital; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology; TMU Research Center of Cancer Translational Medicine; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
Correspondence Address:
Dr. Hung-Yun Lin
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei 11031
 Source of Support: None, Conflict of Interest: None  | 1 |
DOI: 10.4103/JCRP.JCRP_26_19
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Objective: Thyroid hormone plays a vital role in maintaining whole-body physiological activities. However, several different disorders can arise when thyroid hormone is abnormal. Even more, thyroid hormone has been shown to stimulate cancer cell proliferation at physiological concentration. By binding to cell surface integrin αvβ3, thyroid hormone, especially thyroxine activates ERK1/2 activation and sequentially stimulates cell proliferation. Different mechanisms have been demonstrated to be involved in thyroxine-induced cancer proliferation. Checkpoint, PD-1/PD-L1, has shown highly correlated to cancer proliferation and survival. Data Sources: We examined actions of thyroxine and Nano-diamino-tetrac (NDAT; Nanotetrac) on PD-L1 mRNA abundance (qPCR) and PD-L1 protein content in various cancer cells. Methodologies used are qPCR, Western blot analyses, confocal microscopy, and xenograft. Study Selection: We investigate mechanisms involved in thyroid hormone-induced PD-L1 expression and inhibitory effect of NDAT on thyroid hormone-induced PD-L1 expression. Either blocking thyroid hormone-binding on integrin αvβ3 or using NDAT can inhibit PD-L1 expression. Results: Our studies indicate that thyroid hormone induces PD-L1 expression via activating ERK1/2, PI3K, and STAT3 in different types of cancer cells. NDAT inhibits the cancer cell PI3-K and MAPK signal transduction pathways that are critical to PD-L1 gene expression. Other studies on PubMed also indicate thyroxine's actions are via integrin αvβ3. Conclusions: Thyroid hormone-induced PD-L1 expression not only facilitates cancer cell proliferation but also interferes with chemotherapy. In this current review, we will discuss mechanisms involved in thyroid hormone-induced PD-L1 expression. In addition, role of PD-L1 in thyroid hormone-induced cancer growth and metastasis will be addressed.
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