Dickkopf-4 is frequently down-regulated and inhibits growth of colorectal cancer cells.
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.
Baehs
Sebastian
S
Department of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, Munich, Germany.
Herbst
Andreas
A
Thieme
Susanne E
SE
Perschl
Claudia
C
Behrens
Andrea
A
Scheel
Silvio
S
Jung
Andreas
A
Brabletz
Thomas
T
Göke
Burkhard
B
Blum
Helmut
H
Kolligs
Frank T
FT
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
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