Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion

Vasily Vasko, Allan V. Espinosa, William Scouten, Hulling He, Herbert Auer, Sandya Liyanarachchi, Alexander Larin, Victoria Savchenko, Gary L. Francis, Albert De La Chapelle, Motoyasu Saji, Matthew D. Ringel

Research output: Contribution to journalArticle

225 Scopus citations

Abstract

Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison with the central regions of primary PTCs, the invasive fronts overexpressed TGF β, NFκB and integrin pathway members, and regulators of small G proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 34 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required both for the development and maintenance of a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.

Original languageEnglish (US)
Pages (from-to)2803-2808
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number8
DOIs
StatePublished - Feb 20 2007
Externally publishedYes

Keywords

  • Thyroid cancer
  • Vimentin
  • cdc42
  • runx2

ASJC Scopus subject areas

  • General

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