NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE17623 Query DataSets for GSE17623
Status Public on Aug 13, 2009
Title The kinase TNIK is an essential activator of Wnt target genes
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Wnt signalling maintains the undifferentiated state of intestinal crypt/progenitor cells through the TCF4/ß-catenin activating transcriptional complex. In colorectal cancer, activating mutations in Wnt pathway components lead to inappropriate activation of the TCF4/ß-catenin transcriptional program and tumourigenesis in the gut epithelium. The mechanisms by which TCF4/ß-catenin activate key target genes are not well understood. Using a proteomics approach, we identified Tnik, a member of the Germinal centre kinase family, as a Tcf4 interactor in the proliferative crypts of mouse small intestine. Tnik is recruited to promoters of Wnt target genes in mouse crypts and in Ls174T colorectal cancer cells in a ß-catenin dependent manner. Depletion of TNIK and expression of TNIK kinase mutants abrogated TCF-LEF transcription, highlighting the essential role of the kinase activity in Wnt target gene activation. siRNA depletion of TNIK followed by expression array analysis demonstrated that TNIK is an essential and exclusive activator of Wnt induced transcriptional program. As an essential component in the TCF4/ß-catenin activator complex, the kinase TNIK may present an attractive candidate for drug targeting in colorectal cancer.
 
Overall design HEK293T cells: Wnt3A vs control medium (CM) induction for 4, 7 and 9 hours; si-TNIK vs si-control after Wnt3A induction at 4 and 7 hours (2 biological replicates for 7 hour time point); dyeswap for each experiment (i.e. 12 arrays in total).
 
Contributor(s) Mahmoudi T, Li VS, Ng SS, Taouatas N, Vries RG, Mohammed S, Heck AJ, Clevers H
Citation(s) 19816403
Submission date Aug 12, 2009
Last update date Feb 22, 2018
Contact name Vivian Li
E-mail(s) vivian.li@crick.ac.uk
Organization name The Francis Crick Institute
Lab Stem Cell and Cancer Biology
Street address 1 Midland Road
City London
ZIP/Postal code NW1 1AT
Country United Kingdom
 
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (12)
GSM439975 +4hr Wnt
GSM439976 +4hr Wnt (dye swap)
GSM439977 +7hr Wnt
Relations
BioProject PRJNA118493

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE17623_RAW.tar 58.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap