TAZ/WWTR1 is overexpressed in papillary thyroid carcinoma

Eur J Cancer. 2011 Apr;47(6):926-33. doi: 10.1016/j.ejca.2010.11.008. Epub 2010 Dec 3.

Abstract

In this study, we analysed the expression of the transcriptional coactivator TAZ (transcriptional co-activator with PDZ-binding motif), also named WWTR1, in a panel of papillary thyroid carcinoma samples and we observed a significant deregulation of its expression in such tumours. Specifically, by quantitative real-time PCR (qRT-PCR) we evaluated TAZ mRNA levels in tissue specimens (n=61) of papillary thyroid carcinoma (PTC) and herein we show that the PTC samples express much higher TAZ mRNA levels with respect to the normal thyroid tissue (p<0.001). TAZ expression was also evaluated in normal (n=10) and pathological human thyroids (n=17) by immunohistochemical analysis and the increase of TAZ protein levels in PTC was confirmed. To further analyse the molecular mechanisms underlying TAZ overexpression in PTC, we used an inducible system consisting of FRTL-5 rat thyroid cells expressing a conditional RAS oncoprotein and we show that the activation of the RAS signalling pathway is involved in TAZ deregulation. These observations suggest that the activated effectors of the RAS/RAF/MEK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) signalling pathway are involved in the increased expression of TAZ, supporting the idea that this may also occur in thyroid papillary carcinoma. Moreover, we demonstrated that the overexpression of TAZ is able to confer growth advantage to thyroid cells in culture and to induce epithelial-mesenchymal transition. In conclusion, these findings support a potential role for TAZ in the pathogenesis of papillary thyroid carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma
  • Carcinoma, Papillary / etiology*
  • Carcinoma, Papillary / metabolism
  • Cell Division
  • Cell Transformation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Nuclear Receptor Coactivators / metabolism
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins c-ret / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / etiology*
  • Thyroid Neoplasms / metabolism
  • Trans-Activators
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Intracellular Signaling Peptides and Proteins
  • NCOA4 protein, human
  • Nuclear Receptor Coactivators
  • RNA, Messenger
  • TAZ protein, human
  • Trans-Activators
  • Transcription Factors
  • WWTR1 protein, human
  • Proto-Oncogene Proteins c-ret
  • Proto-Oncogene Proteins B-raf