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

Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goektuna SI, Ziegler PK, Canli O, Heijmans J, Huels DJ, Moreaux G, Rupec RA, Gerhard M, Schmid R, Barker N, Clevers H, Lang R, Neumann J, Kirchner T, Taketo MM, Van Den Brink GR, Sansom OJ, Arkan MC, Greten FR (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Cell Elsevier

Book Volume: 152

Pages Range: 25-38

Journal Issue: 1-2

DOI: 10.1016/j.cell.2012.12.012

Abstract

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.

Authors with CRIS profile

Roland Lang Professur für Angeborene Immunität und Pathogenerkennung

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Academic Medical Centre / Academisch Medisch Centrum (AMC) NL Netherlands (NL) Kyoto University / 京都大学 Kyōto daigaku JP Japan (JP) Cancer Research UK Beatson Institute GB United Kingdom (GB) Institute of Medical Biology (IMB) SG Singapore (SG) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universiteit Utrecht (UU) / Utrecht University NL Netherlands (NL)

How to cite

APA:

Schwitalla, S., Fingerle, A.A., Cammareri, P., Nebelsiek, T., Goektuna, S.I., Ziegler, P.K.,... Greten, F.R. (2013). Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell, 152(1-2), 25-38. https://doi.org/10.1016/j.cell.2012.12.012

MLA:

Schwitalla, Sarah, et al. "Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties." Cell 152.1-2 (2013): 25-38.

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