Thyroid hormone actions in liver cancer

Cell Mol Life Sci. 2013 Jun;70(11):1915-36. doi: 10.1007/s00018-012-1146-7. Epub 2012 Sep 6.

Abstract

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 T3/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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Models, Genetic
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / metabolism
  • Receptors, Thyroid Hormone / physiology*
  • Signal Transduction
  • Triiodothyronine / genetics
  • Triiodothyronine / metabolism
  • Triiodothyronine / physiology*

Substances

  • Receptors, Thyroid Hormone
  • Triiodothyronine