Year-end Sale % OFF 
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.
Highlights
The transdifferentiation of epithelial tumor cells towards a mesenchymal condition is a complex process that allows tumor cells to leave their original site and to invade adjacent tissues
Two different doses of transforming growth factor-β (TGF-β) (5 ng/ml and 100 ng/ml) were given to cells for 24h, after which changes in the expression levels of established epithelial-mesenchymal transition (EMT) markers and CDH6 were measured by means of qRT-PCR (Figure 1)
Two epithelial markers - E-CAD and Cadherin-16 (CDH16) - and four mesenchymal markers - NCAD, Tenascin C (TNC), Vimentin (VIM) and Fibronectin 1 (FN1) - were analyzed to monitor the activation of the EMT program [8,22,23,24]
Summary
The transdifferentiation of epithelial tumor cells towards a mesenchymal condition is a complex process that allows tumor cells to leave their original site and to invade adjacent tissues. During this transition ( known as epithelial-mesenchymal transition - EMT), the epithelial cells shed their differentiated characteristics, including cell-cell adhesion, polarity, and lack of motility, and acquire instead mesenchymal features, including motility, invasiveness, and resistance to apoptosis. In spite of its role in promoting the epithelial phenotype during embryogenesis, CDH6 has been described as strongly expressed in ovarian cancer and renal carcinoma [14,15]. We showed that CDH6 is strongly induced by TGF-β treatment both in normal and tumor thyroid cells, and that its expression accompanies invasiveness in human thyroid tumor patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
