Discoidin domain receptor 1 (DDR1), a promising biomarker, induces epithelial to mesenchymal transition in renal cancer cells
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Discoidin domain receptor I (DDR1) is confirmed as a receptor tyrosine kinase (RTK), which plays a consequential role in a variety of cancers. Nevertheless, the influence of DDR1 expression and development in renal clear cell carcinoma (RCCC) are still not well corroborated. In our research, we firstly discovered that the expression level of DDR1 was remarkable related to TNM stage (p = 0.032), depth of tumor invasion (p = 0.047), and lymph node metastasis (p = 0.034) in 119 RCCC tissue samples using tissue microarray. The function of DDR1 was then evaluated in vitro using collagen I and DDR1 small interfering RNA (siRNA) to regulate the expression of DDR1 in OS-RC-2 and ACHN renal cancer cells (RCC). DDR1 expression correlated with increased RCC cell migration, invasion, and angiogenesis. Further study revealed that high expression of DDR1 can result in epithelial to mesenchymal transition (EMT) activation. Western blot assay showed that the N-cadherin protein and vimentin were induced while E-cadherin was reduced after DDR1 over expression. Our results suggest that DDR1 is both a prognostic marker for RCCC and a potential functional target for therapy.
KeywordsDDR1 EMT Biomarker Renal cancer cells
This study is supported by National Natural Science Foundation of China (NSFC), No.81301806; Jiangsu Planned Projects for Postdoctoral Research Funds, No.1501060A; six talent peaks project in Jiangsu Province, No.WSW-056.
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Conflicts of interest
- 10.Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, Scurry J, Scolyer RA, Davies MJ, et al. Overexpression of the cell adhesion molecules ddr1, claudin 3, and ep-cam in metaplastic ovarian epithelium and ovarian cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2004;10:4427–36.CrossRefGoogle Scholar
- 24.L’Hote CG, Thomas PH, Ganesan TS. Functional analysis of discoidin domain receptor 1: effect of adhesion on ddr1 phosphorylation. FASEB J Off Publ Fed Am Soc Exp Biol. 2002;16:234–6.Google Scholar
- 25.Alves F, Saupe S, Ledwon M, Schaub F, Hiddemann W, Vogel WF. Identification of two novel, kinase-deficient variants of discoidin domain receptor 1: differential expression in human colon cancer cell lines. FASEB J Off Publ Fed Am Soc Exp Biol. 2001;15:1321–3.Google Scholar
- 28.Laval S, Butler R, Shelling AN, Hanby AM, Poulsom R, Ganesan TS. Isolation and characterization of an epithelial-specific receptor tyrosine kinase from an ovarian cancer cell line. Cell Growth Differ Mol Biol J Am Assoc Cancer Res. 1994;5:1173–83.Google Scholar