LPS Upregulated VEGFR-3 Expression Promote Migration and Invasion in Colorectal Cancer via a Mechanism of Increased NF-κB Binding to the Promoter of VEGFR-3

Abstract

Background and Aim: Lipopolysaccharide(LPS) could promote the progression of colorectal cancer, but the specific regulatory mechanisms are largely unknown. So, this study aim to clarify the mechanisms that LPS upregulated VEGFR-3, which promotes colorectal cancer cells migration and invasion with a mechanism of increased NF-κB bind to the promoter of VEGFR-3. Methods: The present study examined the VEGFR-3 expression in colorectal cancer tissues and analyzed the relationship between the VEGFR-3 expression with clinical parameters. PCR, Western blot, CCK-8, colone formation assay, and Transwell assay detected that LPS promoted the migration and invasion and the role of VEGFR-3 in the process of colorectal carcinoma in vitro. Used the methods of promoter analysis, EMSA assay and ChIP assay to explore the mechanisms LPS increased the expression of VEGFR-3. Results: VEGFR-3 was significantly high expression in the colorectal cancer tissues. And the high expression was associated with the TNM stage and lymph node metastasis of colorectal cancer. LPS could promote the migration and invasion, which could be blocked by the neutralizing antibody IgG of VEGFR-3. And found that -159 nt to +65 nt was the crucial region of VEGFR-3 promoter. And detected that the NF-κB was important transcription factor for the VEGFR-3 promoter. And LPS could increase NF-κB binding to VEGFR-3 promoter and upregulated the expression of VEGFR-3 to exert biological functions. Conclusion: We have elucidated the relationship between LPS and the VEGFR-3 expression and revealed that VEGFR-3 play very important role in the process of LPS promoting the migration and invasion of colorectal cancer cells. Further illuminated the mechanism that LPS upregulated VEGFR-3 expression via increased NF-κB bind to the promoter of VEGFR-3.