Down-regulation of CXCL1 inhibits tumor growth in colorectal liver metastasis

Cytokine. 2012 Jan;57(1):46-53. doi: 10.1016/j.cyto.2011.10.019. Epub 2011 Nov 29.


As part of ongoing studies to obtain a global picture of invasion related events in colorectal liver metastases, here, we report our findings on gene expression of the pro-angiogenic subgroup of chemokines, the CXCL-ELR+ chemokines. Apart from their pro-angiogenic and chemoattractant function, these chemokines appear to also contribute to tumor cell transformation, growth and invasion. In our nude mouse model of colorectal liver metastases, we found CXCL1,2,3,5 and 8 (IL-8) to be up-regulated in the tumor cells of the invasion front as compared to the tumor cells in the inner parts of the tumor. ShRNA mediated down-regulation of the most prominently up-regulated group member, CXCL1/gro-alpha resulted in inhibition of cell viability, invasion and proliferation. In vivo, down-regulation of CXCL1 resulted in a nearly complete prevention of tumor growth in nude mice. Mechanistically, auto-regulatory mechanisms involving NF-kappaB and Akt appear to be involved in pro-tumorigenic functions of CXCL1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Chemokine CXCL1 / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary*
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Up-Regulation / genetics


  • CXCL1 protein, human
  • Chemokine CXCL1
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt