X-box binding protein 1 (XBP-1) enhances colorectal cancer cell invasion

Abstract

In this study, we investigated the role of X-box binding protein 1 (XBP-1) and vascular endothelial growth factor receptor-2 (VEGF-R2) signalling in colorectal cancer (CRC) cells invasion by evaluating their extent of activation in CRC tissues and cell lines using immunohistochemistry, western blotting, and invasion assays. Results showed that XBP-1 is expressed at high levels in metastatic and poorly differentiated tissue samples, whereas it appeared relatively low in moderately and well-differentiated tissue samples compared to those in normal colon tissue. The XBP-1 immunoreactivity score (IRS) was positively associated with increasing tumour invasion. In vitro studies showed that overexpression of XBP-1 promoted cancer cell invasion, which was suppressed by inhibition of XBP-1 using small interfering RNA molecules (siRNA). Inhibition of XBP-1 expression significantly decreased levels of VEGF-R2.In conclusion, XBP-1 might be regarded as a novel predictive biomarker in CRC invasion and metastasis.

Keywords:

• Colorectal cancer
• Invasion
• Metastasis
• XBP-1
• VEGF-R2
• UPR
• Chemotherapy
• 5-FU