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

Schwitalla, S. et al. (2013) Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell, 152(1-2), pp. 25-38. (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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Moreaux, Ms Guenievre and Cammareri, Dr Patrizia and Huels, Mr David and Sansom, Professor Owen
• Authors: Schwitalla, S., Fingerle, A.A., Cammareri, P., Nebelsiek, T., Göktuna, S.I., Ziegler, P.K., Canli, O., Heijmans, J., Huels, D.J., Moreaux, G., Rupec, R.A., Gerhard, M., Schmid, R., Barker, N., Clevers, H., Lang, R., Neumann, J., Kirchner, T., Taketo, M.M., van den Brink, G.R., Sansom, O.J., Arkan, M.C., and Greten, F.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell
• ISSN: 0092-8674