Abstract

Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared to that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3β/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment. Graphical What's new? While molecular mechanisms underlying therapeutic failure and the progression of colorectal cancer (CRC) are not fully understood, signaling pathways mediated by tyrosine kinase receptors often influence cell proliferation and differentiation. Here, the authors investigated the relevance of discoidin domain receptor 2 (DDR2), a novel transmembrane receptor tyrosine kinase, in CRC. In experiments in vitro and in vivo, DDR2 overexpression was found to induce epithelial mesenchymal transition and to increase metastatic capacity in CRC cells. These metastatic effects resulted from DDR2 activation of the AKT/GSK-3β/Slug signaling pathway. The findings identify DDR2 as a promising therapeutic target for metastatic CRC.