Acting at a cell surface receptor on the extracellular domain of integrin ..., thyroid\nhormone analogues regulate downstream the expression of a large panel of genes relevant to cancer\ncell proliferation, to cancer cell survival pathways, and to tumor-linked angiogenesis. Because ... is involved in the cancer cell metastatic process, we examine here the possibility that thyroid hormone\nas L-thyroxine (T4) and the thyroid hormone antagonist, tetraiodothyroacetic acid (tetrac), may\nrespectively promote and inhibit metastasis. Actions of T4 and tetrac that are relevant to cancer\nmetastasis include the multitude of synergistic effects on molecular levels such as expression of matrix\nmetalloproteinase genes, angiogenesis support genes, receptor tyrosine kinase (EGFR/ERBB2) genes,\nspecific microRNAs, the epithelialâ??mesenchymal transition (EMT) process; and on the cellular level\nare exemplified by effects on macrophages. We conclude that the thyroid hormone .... interaction\nis mechanistically linked to cancer metastasis and that modified tetrac molecules have antimetastatic\nactivity with feasible therapeutic potential.
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