Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties

Sarah Schwitalla, Alexander A. Fingerle, Patrizia Cammareri, Tim Nebelsiek, Serkan I. Göktuna, Paul K. Ziegler, Ozge Canli, Jarom Heijmans, David J. Huels, Guenievre Moreaux, Rudolf A. Rupec, Markus Gerhard, Roland Schmid, Nick Barker, Hans Clevers, Roland Lang, Jens Neumann, Thomas Kirchner, Makoto M. Taketo, Gijs R. Van Den BrinkOwen J. Sansom, Melek C. Arkan, Florian R. Greten

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

802 Citaten (Scopus)


Cell-type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor-initiating stem cells and nonstem cells triggered by an inflammatory stroma. NF-κB represents a key transcription factor within the inflammatory tumor microenvironment. However, NF-κB's function in tumor-initiating cells has not been examined yet. Using a genetic model of intestinal epithelial cell (IEC)-restricted constitutive Wnt-activation, which comprises the most common event in the initiation of colon cancer, we demonstrate that NF-κB modulates Wnt signaling and show that IEC-specific ablation of RelA/p65 retards crypt stem cell expansion. In contrast, elevated NF-κB signaling enhances Wnt activation and induces dedifferentiation of nonstem cells that acquire tumor-initiating capacity. Thus, our data support the concept of bidirectional conversion and highlight the importance of inflammatory signaling for dedifferentiation and generation of tumor-initiating cells in vivo. PaperFlick:

Originele taal-2Engels
Pagina's (van-tot)25-38
Aantal pagina's14
Nummer van het tijdschrift1-2
StatusGepubliceerd - 7 jan. 2013
Extern gepubliceerdJa


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