Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.

Matilde Todaro, Giorgio Stassi, Louis Vermeulen, Christian Merz, Tijana Borovski, Kate Cameron, Felipe De Sousa E Melo, Maartje Van Der Heijden, Martin R. Sprick, Jurriaan B. Tuynman, Hans Rodermond, Giorgio Stassi, Dick J. Richel, Jan Paul Medema, Joan H. De Jong, Kristel Kemper

Risultato della ricerca: Articlepeer review

1258 Citazioni (Scopus)


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.
Lingua originaleEnglish
pagine (da-a)468-476
Numero di pagine9
RivistaNature Cell Biology
Stato di pubblicazionePublished - 2010

All Science Journal Classification (ASJC) codes

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