DDR1 enhances invasion and metastasis of gastric cancer via epithelial-mesenchymal transition

Abstract

In this study, we investigated the effects of DDR1 on the invasion and metastasis in gastric cancer (GC) via epithelial-mesenchymal transition (EMT). Immunohistochemistry analysis was used to detect DDR1, E-cadherin, and Vimentin expression in GC tissues as well as DDR1 expression in GC cell lines and normal gastric epithelial cells. The relationship between DDR1 expression and EMT in GC cell lines was explored by down and upregulating DDR1 and examining corresponding changes in the expression of EMT-related proteins and in biological characteristics. Furthermore, a nude mice model with a transplantation tumor generating from stably transfected GC cells with DDR1 overexpression was established and performed to further reveal the effects of DDR1 expression on cellular morphology and growth of GC. Our results showed that DDR1 was highly expressed in GC tissues and cell lines compared with adjacent tissues and normal cell line, and its expression was significantly higher in GC having poor differentiation (p < 0.01), advanced depth of wall invasion (p = 0.020), lymph node metastasis (p = 0.0001), liver metastasis (p < 0.01), and high TNM stage (p < 0.01). Western blot analyses revealed that DDR1 overexpression resulted in a significant decrease in the expression of E-cadherin (p < 0.01) and an increase in the expression of Vimentin and Snail (p < 0.01), while knockdown of DDR1 led to opposite outcomes. We further demonstrated that DDR1 overexpression promoted GC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01), and accelerated the growth (p < 0.05) as well as the microvessel formation (p < 0.01) of transplantation tumor in nude mice. Our study establishes that DDR1 enhances invasion and metastasis of gastric cancer via EMT.

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