ROS Production and NF-κB Activation Triggered by RAC1 Facilitate WNT-driven Intestinal Stem Cell Proliferation and Colorectal Cancer Initiation

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 May 14

PMID 23665120

Citations 201

Authors

Kevin B Myant

Patrizia Cammareri

Ewan J McGhee

Rachel A Ridgway

David J Huels

Julia B Cordero

Sarah Schwitalla

Gabriela Kalna

Erinn-Lee Ogg

Dimitris Athineos

Paul Timpson

Marcos Vidal

Graeme I Murray

Florian R Greten

Kurt I Anderson

Owen J Sansom

Affiliations

Soon will be listed here.

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.

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