PMID- 20418870
OWN - NLM
STAT- MEDLINE
DCOM- 20100729
LR  - 20240109
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Linking)
VI  - 12
IP  - 5
DP  - 2010 May
TI  - Wnt activity defines colon cancer stem cells and is regulated by the 
      microenvironment.
PG  - 468-76
LID - 10.1038/ncb2048 [doi]
AB  - Despite the presence of mutations in APC or beta-catenin, which are believed to 
      activate the Wnt signalling cascade constitutively, most colorectal cancers show 
      cellular heterogeneity when beta-catenin localization is analysed, indicating a 
      more complex regulation of Wnt signalling. We explored this heterogeneity with a 
      Wnt reporter construct and observed that high Wnt activity functionally 
      designates the colon cancer stem cell (CSC) population. In adenocarcinomas, high 
      activity of the Wnt pathway is observed preferentially in tumour cells located 
      close to stromal myofibroblasts, indicating that Wnt activity and cancer stemness 
      may be regulated by extrinsic cues. In agreement with this notion, 
      myofibroblast-secreted factors, specifically hepatocyte growth factor, activate 
      beta-catenin-dependent transcription and subsequently CSC clonogenicity. More 
      significantly, myofibroblast-secreted factors also restore the CSC phenotype in 
      more differentiated tumour cells both in vitro and in vivo. We therefore propose 
      that stemness of colon cancer cells is in part orchestrated by the 
      microenvironment and is a much more dynamic quality than previously expected that 
      can be defined by high Wnt activity.
FAU - Vermeulen, Louis
AU  - Vermeulen L
AD  - Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for 
      Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University 
      of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
FAU - De Sousa E Melo, Felipe
AU  - De Sousa E Melo F
FAU - van der Heijden, Maartje
AU  - van der Heijden M
FAU - Cameron, Kate
AU  - Cameron K
FAU - de Jong, Joan H
AU  - de Jong JH
FAU - Borovski, Tijana
AU  - Borovski T
FAU - Tuynman, Jurriaan B
AU  - Tuynman JB
FAU - Todaro, Matilde
AU  - Todaro M
FAU - Merz, Christian
AU  - Merz C
FAU - Rodermond, Hans
AU  - Rodermond H
FAU - Sprick, Martin R
AU  - Sprick MR
FAU - Kemper, Kristel
AU  - Kemper K
FAU - Richel, Dick J
AU  - Richel DJ
FAU - Stassi, Giorgio
AU  - Stassi G
FAU - Medema, Jan Paul
AU  - Medema JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100425
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
CIN - Nat Cell Biol. 2010 May;12(5):419-21. PMID: 20418873
CIN - Nat Rev Cancer. 2010 Jun;10(6):386. PMID: 20509174
MH  - Animals
MH  - Coculture Techniques
MH  - Colonic Neoplasms/metabolism/*pathology
MH  - Fibroblasts/pathology
MH  - Hepatocyte Growth Factor/metabolism/physiology
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Proteins
MH  - Neoplasms, Experimental
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - *Paracrine Communication
MH  - Signal Transduction
MH  - Transplantation, Heterologous
MH  - Wnt Proteins/*metabolism
MH  - beta Catenin
EDAT- 2010/04/27 06:00
MHDA- 2010/07/30 06:00
CRDT- 2010/04/27 06:00
PHST- 2010/01/22 00:00 [received]
PHST- 2010/03/26 00:00 [accepted]
PHST- 2010/04/27 06:00 [entrez]
PHST- 2010/04/27 06:00 [pubmed]
PHST- 2010/07/30 06:00 [medline]
AID - ncb2048 [pii]
AID - 10.1038/ncb2048 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2010 May;12(5):468-76. doi: 10.1038/ncb2048. Epub 2010 Apr 25.