title: Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Medicine MOMA, Center for Molecular Clinical Cancer Research, Aarhus University Hospital/Skejby, DK-8200 Aarhus N, Denmark. kbdr@ki.au.dk, www.mdl.dk
authors.forename: K
authors.initials: K
authors.lastname: Birkenkamp-Demtroder
authors.forename: A
authors.initials: A
authors.lastname: Maghnouj
authors.forename: F
authors.initials: F
authors.lastname: Mansilla
authors.forename: K
authors.initials: K
authors.lastname: Thorsen
authors.forename: C L
authors.initials: CL
authors.lastname: Andersen
authors.forename: B
authors.initials: B
authors.lastname: Øster
authors.forename: S
authors.initials: S
authors.lastname: Hahn
authors.forename: T F
authors.initials: TF
authors.lastname: Ørntoft
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006821:Hyaluronoglucosaminidase; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009367:Neoplasm Staging; D040081:Protein Array Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins; D051153:Wnt Proteins; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase