Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells

Br J Cancer. 2011 Aug 9;105(4):552-61. doi: 10.1038/bjc.2011.268. Epub 2011 Jul 19.


Background: The KIAA1199 transcript is upregulated in colon adenomas and downregulated upon β-catenin knockdown.

Methods: Transcript profiling was performed on >500 colon biopsies, methylation profiling data were compared with transcript data. Immunohistochemistry assessed KIAA1199 protein expression in 270 stage II/III tumours (>3 years follow-up). The effects of stable KIAA1199 knockdown in SW480 cells (three different constructs) were studied using transcriptional profiling, proliferation and protein analysis.

Results: The KIAA1199 transcript was strongly upregulated in 95% of adenocarcinomas. Absent expression in normal mucosa correlated with KIAA1199 promotor methylation. Nuclear and cytoplasmic KIAA1199 protein expression was identified in colon adenocarcinomas and other types of cancers. A subpopulation of patients with tumours strongly expressing KIAA1199 in the nucleus showed a better outcome with regard to recurrence as lung or liver metastases. The KIAA1199 knockdown affected the cell cycle and the Wnt-signalling pathway. Reduced cellular proliferation and decreased KI67, phosphorylated retinoblastoma, β-catenin and ASCL2 protein expression supported these findings. Eighteen Wnt-signalling genes differentially expressed upon KIAA1199 knockdown correlated with the KIAA1199 expression profile in clinical specimens.

Conclusion: The KIAA1199 knockdown attenuates the effects of the Wnt/β-catenin signalling and it may thus be regarded as a regulatory part of this pathway.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronoglucosaminidase
  • Immunohistochemistry
  • Microscopy, Fluorescence
  • Neoplasm Staging
  • Protein Array Analysis
  • Proteins / genetics
  • Proteins / metabolism*
  • Signal Transduction*
  • Up-Regulation
  • Wnt Proteins / metabolism*


  • Proteins
  • Wnt Proteins
  • CEMIP protein, human
  • Hyaluronoglucosaminidase