The thyroid hormone 3,3′,5-triiodo-l-thyronine (T3) mediates several physiological processes, including embryonic development, cellular differentiation, metabolism, and the regulation of cell proliferation. Thyroid hormone receptors (TRs) generally act as heterodimers with the retinoid X receptor (RXR) to regulate target genes. In addition to their developmental and metabolic functions, TRs have been shown to play a tumor suppressor role, suggesting that their aberrant expression can lead to tumor transformation. Conversely, recent reports have shown an association between overexpression of wild-type TRs and tumor metastasis. Signaling crosstalk between T3/TR and other pathways or specific TR coregulators appear to affect tumor development. Since TR actions are complex as well as cell context-, tissue- and time-specific, aberrant expression of the various TR isoforms has different effects during diverse tumorigenesis. Therefore, elucidation of the T 3/TR signaling mechanisms in cancers should facilitate the identification of novel therapeutic targets. This review provides a summary of recent studies focusing on the role of TRs in hepatocellular carcinomas (HCCs).
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