Cathepsin H regulated by the thyroid hormone receptors associate with tumor invasion in human hepatoma cells

S. M. Wu, Y. H. Huang, C. T. Yeh, M. M. Tsai, C. H. Liao, W. L. Cheng, W. J. Chen, K. H. Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

42 Scopus citations


Thyroid hormone, 3, 3′, 5-triiodo-L-thyronine (T 3), mediates cell growth, development and differentiation by binding to its nuclear receptors (TRs). The role of TRs in cancer is still undefined. Notably, hyperthyroxinemia has been reported to influence the rate of colon cancer in an experimental model of carcinogenesis in rats. Previous microarray analysis revealed that cathepsin H (CTSH) is upregulated by T 3 in HepG2-TR cells. We verified that mRNA and protein expression of CTSH are induced by T 3 in HepG2-TR cells and in thyroidectomized rats following administration of T 3. The possible thyroid hormone-responsive elements of the CTSH promoter localized to the nucleotides-2038 to-1966 and-1565 to-1501 regions. An in vitro functional assay showed that CTSH can increase metastasis. J7 cells overexpressing CTSH were inoculated into severe combined immune-deficient mice and these J7-CTSH mice displayed a greater metastatic potential than did J7-control mice. The clinicopathologic significance of CTSH expression in hepatocellular carcinoma (HCC) was also investigated. The CTSH overexpressing in HCC was associated with the presence of microvascular invasion (P0.037). The microvascular invasion characteristic is closely related to our in vitro characterization of CTSH function. Our results show that T 3-mediated upregulation of CTSH led to matrix metallopeptidase or extracellular signal-regulated kinase activation and increased cell migration. This study demonstrated that CTSH overexpression in a subset hepatoma may be TR dependent and suggests that this overexpression has an important role in hepatoma progression.

Original languageEnglish
Pages (from-to)2057-2069
Number of pages13
Issue number17
StatePublished - 28 04 2011
Externally publishedYes


  • cysteine proteases
  • hepatocellular carcinoma
  • migration
  • receptors


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