PMID- 17785439
OWN - NLM
STAT- MEDLINE
DCOM- 20071128
LR  - 20220317
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 27
IP  - 21
DP  - 2007 Nov
TI  - Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of 
      intestinal stem cells.
PG  - 7551-9
AB  - The Wnt signaling pathway is deregulated in over 90% of human colorectal cancers. 
      beta-Catenin, the central signal transducer of the Wnt pathway, can directly 
      modulate gene expression by interacting with transcription factors of the TCF/LEF 
      family. In the present study we investigate the role of Wnt signaling in the 
      homeostasis of intestinal epithelium by using tissue-specific, inducible 
      beta-catenin gene ablation in adult mice. Block of Wnt/beta-catenin signaling 
      resulted in rapid loss of transient-amplifying cells and crypt structures. 
      Importantly, intestinal stem cells were induced to terminally differentiate upon 
      deletion of beta-catenin, resulting in a complete block of intestinal homeostasis 
      and fatal loss of intestinal function. Transcriptional profiling of mutant crypt 
      mRNA isolated by laser capture microdissection confirmed those observations and 
      allowed us to identify genes potentially responsible for the functional 
      preservation of intestinal stem cells. Our data demonstrate an essential 
      requirement of Wnt/beta-catenin signaling for the maintenance of the intestinal 
      epithelium in the adult organism. This challenges attempts to target aberrant Wnt 
      signaling as a new therapeutic strategy to treat colorectal cancer.
FAU - Fevr, Tea
AU  - Fevr T
AD  - Ecole Polytechnique Federale de Lausanne, ISREC (Swiss Institute for Experimental 
      Cancer Research), Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
FAU - Robine, Sylvie
AU  - Robine S
FAU - Louvard, Daniel
AU  - Louvard D
FAU - Huelsken, Joerg
AU  - Huelsken J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070904
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Biomarkers)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cell Death
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cell Proliferation
MH  - Down-Regulation
MH  - *Homeostasis
MH  - Intestinal Mucosa/cytology/metabolism/ultrastructure
MH  - Intestines/*cytology/*physiology/ultrastructure
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Signal Transduction
MH  - Stem Cells/*cytology/metabolism
MH  - Transcription, Genetic
MH  - Wnt Proteins/*metabolism
MH  - beta Catenin/deficiency/*metabolism
PMC - PMC2169070
EDAT- 2007/09/06 09:00
MHDA- 2007/12/06 09:00
PMCR- 2008/03/01
CRDT- 2007/09/06 09:00
PHST- 2007/09/06 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/09/06 09:00 [entrez]
PHST- 2008/03/01 00:00 [pmc-release]
AID - MCB.01034-07 [pii]
AID - 1034-07 [pii]
AID - 10.1128/MCB.01034-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2007 Nov;27(21):7551-9. doi: 10.1128/MCB.01034-07. Epub 2007 Sep 
      4.