PMID- 19251639
OWN - NLM
STAT- MEDLINE
DCOM- 20090512
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 15
DP  - 2009 Apr 14
TI  - Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis 
      in the intestine.
PG  - 6309-14
LID - 10.1073/pnas.0900427106 [doi]
AB  - Notch and Wnt signals play essential roles in intestinal development and 
      homeostasis, yet how they integrate their action to affect intestinal 
      morphogenesis is not understood. We examined the interplay between these two 
      signaling pathways in vivo, by modulating Notch activity in mice carrying either 
      a loss- or a gain-of-function mutation of Wnt signaling. We find that the 
      dramatic proliferative effect that Notch signals have on early intestinal 
      precursors requires normal Wnt signaling, whereas its influence on intestinal 
      differentiation appears independent of Wnt. Analogous experiments in Drosophila 
      demonstrate that the synergistic effects of Notch and Wnt are valid across 
      species. We also demonstrate a striking synergy between Notch and Wnt signals 
      that results in inducing the formation of intestinal adenomas, particularly in 
      the colon, a region rarely affected in available mouse tumor models, but the 
      primary target organ in human patients. These studies thus reveal a previously 
      unknown oncogenic potential of Notch signaling in colorectal tumorigenesis that, 
      significantly, is supported by the analysis of human tumors. Importantly, our 
      experimental evidence raises the possibility that Notch activation might be an 
      essential initial event triggering colorectal cancer.
FAU - Fre, Silvia
AU  - Fre S
AD  - Morphogenesis and Intracellular Signaling, Institut Curie-Unite Mixte de 
      Recherche 144 Centre National de la Recherche Scientifique, 75248 Paris Cedex 05, 
      France.
FAU - Pallavi, S K
AU  - Pallavi SK
FAU - Huyghe, Mathilde
AU  - Huyghe M
FAU - Lae, Marick
AU  - Lae M
FAU - Janssen, Klaus-Peter
AU  - Janssen KP
FAU - Robine, Sylvie
AU  - Robine S
FAU - Artavanis-Tsakonas, Spyros
AU  - Artavanis-Tsakonas S
FAU - Louvard, Daniel
AU  - Louvard D
LA  - eng
GR  - CA098402/CA/NCI NIH HHS/United States
GR  - R37 NS026084/NS/NINDS NIH HHS/United States
GR  - R01 NS026084/NS/NINDS NIH HHS/United States
GR  - R01 CA098402/CA/NCI NIH HHS/United States
GR  - NS26084/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090227
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Notch)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (Tcf4 protein, mouse)
RN  - 0 (Transcription Factor 4)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt1 Protein)
RN  - 0 (wg protein, Drosophila)
SB  - IM
MH  - Adenoma/genetics/metabolism/pathology
MH  - Animals
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/genetics/*metabolism/*pathology
MH  - Drosophila Proteins/genetics/metabolism
MH  - Drosophila melanogaster
MH  - Humans
MH  - Intestinal Neoplasms/genetics/*metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/deficiency/genetics/metabolism
MH  - Receptors, Notch/genetics/*metabolism
MH  - *Signal Transduction
MH  - Survival Rate
MH  - TCF Transcription Factors/deficiency/genetics/metabolism
MH  - Transcription Factor 4
MH  - Wnt Proteins/*metabolism
MH  - Wnt1 Protein/genetics/metabolism
PMC - PMC2649205
COIS- The authors declare no conflict of interest.
EDAT- 2009/03/03 09:00
MHDA- 2009/05/13 09:00
PMCR- 2009/02/27
CRDT- 2009/03/03 09:00
PHST- 2009/03/03 09:00 [entrez]
PHST- 2009/03/03 09:00 [pubmed]
PHST- 2009/05/13 09:00 [medline]
PHST- 2009/02/27 00:00 [pmc-release]
AID - 0900427106 [pii]
AID - 7065 [pii]
AID - 10.1073/pnas.0900427106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6309-14. doi: 
      10.1073/pnas.0900427106. Epub 2009 Feb 27.