DDR2 facilitates papillary thyroid carcinoma epithelial mesenchymal transition by activating ERK2/Snail1 pathway

The upregulation of Discoidin Domain Receptor tyrosine kinase 2 (DDR2) has been reported to be associated with poor prognosis and metastasis in numerous tumor types by inducing epithelial-mesenchymal transition (EMT); however, the expression profile of DDR2 in papillary thyroid carcinoma (PTC) with local metastasis and the effect of DDR2 on PTC cells remain unknown. The aim of the present study was to investigate the expression levels of DDR2 in tumor tissues of patients with PTC with local metastasis and cell lines and to determine the effect of DDR2 on EMT in PTC cells. In the present study, it was demonstrated that DDR2 was significantly increased in tumor tissues of patients with PTC with local metastasis and human PTC cell lines. The overexpression of DDR2 by lentiviral transfection decreased E-cadherin protein, increased Vimentin protein, and promoted cell migration and invasion. The inhibition of DDR2 reversed transforming growth factor-β- and collagen I-induced EMT. EMT induced by DDR2 overexpression was suggested to be dependent on increased Snail1 protein level following extracellular signal-regulated kinase (ERK)2 activation. The inhibition of Snail1 or ERK2 was sufficient to abrogate DDR2-induced PTC cell EMT. In conclusion, these results indicate that DDR2 is upregulated in PTC tissues with local metastasis. Overexpression of DDR2 induced EMT in PTC cells by activating ERK2 and stabilizing Snail1, making it a promising therapeutic target for reducing PTC local or distant metastasis.