Cadherin 6 Is a New RUNX2 Target in TGF-β Signalling Pathway

PLoS One. 2013 Sep 12;8(9):e75489. doi: 10.1371/journal.pone.0075489. eCollection 2013.

Abstract

Modifications in adhesion molecules profile may change the way tumor cells interact with the surrounding microenvironment. The Cadherin family is a large group of transmembrane proteins that dictate the specificity of the cellular interactions. The Cadherin switch that takes place during epithelial-mesenchymal transition (EMT) contributes to loosening the rigid organization of epithelial tissues and to enhancing motility and invasiveness of tumor cells. Recently, we found Cadherin-6 (CDH6, also known as K-CAD) highly expressed in thyroid tumor cells that display mesenchymal features and aggressive phenotype, following the overexpression of the transcriptional regulator Id1. In this work, we explored the possibility that CDH6 is part of the EMT program in thyroid tumors. We demonstrate that CDH6 is a new transforming growth factor-β (TGF-β) target and that its expression is modulated similarly to other EMT mesenchymal markers, both in vitro and in thyroid tumor patients. We show for the first time that CDH6 is expressed in human thyroid carcinomas and that its expression is enhanced at the invasive front of the tumor. Finally, we show that CDH6 is under the control of the transcription factor RUNX2, which we previously described as a crucial mediator of the Id1 pro-invasive function in thyroid tumor cells. Overall, these observations provide novel information on the mechanism of the EMT program in tumor progression and indicate CDH6 as a potential regulator of invasiveness in thyroid tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma, Papillary
  • Cell Line
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression
  • Gene Expression Regulation
  • Humans
  • Models, Biological
  • Neoplasm Invasiveness
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Phenotype
  • Signal Transduction* / drug effects
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology

Substances

  • Cadherins
  • Core Binding Factor Alpha 1 Subunit
  • Transforming Growth Factor beta
  • K cadherin

Grant support

This work was supported by grants from the Italian Association for Cancer Research (AIRC, MFAG:10745)(http://www.airc.it/) and the Guido Berlucchi Foundation (http://www.fondazioneberlucchi.com/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.