ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation

Myant, K.B. et al. (2013) ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell, 12(6), pp. 761-773. (doi:10.1016/j.stem.2013.04.006)

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Publisher's URL: http://dx.doi.org/10.1016/j.stem.2013.04.006

Abstract

The Adenomatous Polyposis Coli (APC) gene is mutated in the majority of colorectal cancers (CRCs). Loss of APC leads to constitutively active WNT signaling, hyperproliferation, and tumorigenesis. Identification of pathways that facilitate tumorigenesis after APC loss is important for therapeutic development. Here, we show that RAC1 is a critical mediator of tumorigenesis after APC loss. We find that RAC1 is required for expansion of the LGR5 intestinal stem cell (ISC) signature, progenitor hyperproliferation, and transformation. Mechanistically, RAC1-driven ROS and NF-κB signaling mediate these processes. Together, these data highlight that ROS production and NF-κB activation triggered by RAC1 are critical events in CRC initiation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cammareri, Dr Patrizia and Vidal, Dr Marcos and McGhee, Dr Ewan and Kalna, Dr Gabriela and Cordero, Dr Julia and Myant, Dr Kevin and Anderson, Professor Kurt and Ridgway, Dr Rachel and Timpson, Dr Paul and Sansom, Professor Owen
Authors: Myant, K.B., Cammareri, P., McGhee, E.J., Ridgway, R.A., Huels, D.J., Cordero, J.B., Schwitalla, S., Kalna, G., Ogg, E., Athineos, D., Timpson, P., Vidal, M., Murray, G.I., Greten, F.R., Anderson, K.I., and Sansom, O.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Stem Cell
Publisher:Elsevier
ISSN:1934-5909
ISSN (Online):1875-9777

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