title: Dickkopf-4 is frequently down-regulated and inhibits growth of colorectal cancer cells.
abstract: Like Dickkopf-1 (DKK1), DKK4 is a target of beta-catenin/Tcf-4 in colorectal cancer. However, as a negative regulator of Wnt signalling its function in colorectal cancer cells is not well understood. We report that DKK4 is frequently down-regulated in colorectal cancer cell lines with deregulated beta-catenin/Tcf-4 and in primary colorectal cancers. Exposure of cancer cells to DKK4 strongly inhibits basal beta-catenin/Tcf-4 signalling activity, cancer cell growth and cell cycle progression. Therefore, loss of this negative feed-back loop provides Wnt factor expressing cancer cells with a growth advantage. Our data demonstrate that DKK4 is an important negative regulator of colon cancer cell growth.
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Baehs
authors.forename: Andreas
authors.initials: A
authors.lastname: Herbst
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Thieme
authors.forename: Claudia
authors.initials: C
authors.lastname: Perschl
authors.forename: Andrea
authors.initials: A
authors.lastname: Behrens
authors.forename: Silvio
authors.initials: S
authors.lastname: Scheel
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Helmut
authors.initials: H
authors.lastname: Blum
authors.forename: Frank T
authors.initials: FT
authors.lastname: Kolligs
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D051176:beta Catenin / Q000037:antagonists & inhibitors
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C442333:DKK4 protein, human; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin