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

J Chemother. 2015 Jun;27(3):167-73. doi: 10.1179/1973947815Y.0000000006. Epub 2015 Feb 18.

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: 5-FU; Chemotherapy,; Colorectal cancer,; Invasion,; Metastasis,; UPR,; VEGF-R2,; XBP-1,.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Cell Movement*
  • Cell Proliferation*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Neoplasm Invasiveness
  • RNA, Small Interfering / genetics
  • Regulatory Factor X Transcription Factors
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • X-Box Binding Protein 1

Substances

  • DNA-Binding Proteins
  • RNA, Small Interfering
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Vascular Endothelial Growth Factor Receptor-2