Mousa Shaker A, Glinsky Gennadi V, Lin Hung-Yun, Ashur-Fabian Osnat, Hercbergs Aleck, Keating Kelly A, Davis Paul J
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
Institute of Engineering in Medicine, University of California, San Diego, CA 92093, USA.
Biomedicines. 2018 Aug 22;6(3):89. doi: 10.3390/biomedicines6030089.
Acting at a cell surface receptor on the extracellular domain of integrin αvβ3, thyroid hormone analogues regulate downstream the expression of a large panel of genes relevant to cancer cell proliferation, to cancer cell survival pathways, and to tumor-linked angiogenesis. Because αvβ3 is involved in the cancer cell metastatic process, we examine here the possibility that thyroid hormone as l-thyroxine (T4) and the thyroid hormone antagonist, tetraiodothyroacetic acid (tetrac), may respectively promote and inhibit metastasis. Actions of T4 and tetrac that are relevant to cancer metastasis include the multitude of synergistic effects on molecular levels such as expression of matrix metalloproteinase genes, angiogenesis support genes, receptor tyrosine kinase (/) genes, specific microRNAs, the epithelial⁻mesenchymal transition (EMT) process; and on the cellular level are exemplified by effects on macrophages. We conclude that the thyroid hormone-αvβ3 interaction is mechanistically linked to cancer metastasis and that modified tetrac molecules have antimetastatic activity with feasible therapeutic potential.
甲状腺激素类似物作用于整合素αvβ3细胞外结构域的细胞表面受体，在下游调节大量与癌细胞增殖、癌细胞存活途径以及肿瘤相关血管生成相关的基因表达。由于αvβ3参与癌细胞转移过程，我们在此研究甲状腺激素L-甲状腺素（T4）和甲状腺激素拮抗剂四碘甲状腺乙酸（tetrac）分别促进和抑制转移的可能性。T4和tetrac与癌症转移相关的作用包括在分子水平上对基质金属蛋白酶基因、血管生成支持基因、受体酪氨酸激酶（/）基因、特定微小RNA、上皮-间质转化（EMT）过程等的多种协同作用；在细胞水平上以对巨噬细胞的作用为例。我们得出结论，甲状腺激素-αvβ3相互作用在机制上与癌症转移相关，并且修饰后的tetrac分子具有抗转移活性，具有可行的治疗潜力。
