Colorectal cancer mouse models: integrating inflammation and the stroma
- Author(s)
- Ernst, M; Ramsay, RG;
- Details
- Publication Year 2012-01,Volume 27,Issue #1,Page 39-50
- Journal Title
- Journal of gastroenterology and hepatology
- Publication Type
- Journal Article
- Abstract
- Sequences of molecular events that initiate and advance the progression of human colorectal cancer (CRC) are becoming clearer. Accepting that these events, once they are in place, accumulate over time, rapid disease progression might be expected. Yet CRC usually develops slowly over decades. Emerging insights suggest that the tumor cell microenvironment encompassing fibroblasts and endothelial and immune cells dictate when, whether, and how malignancies progress. Signaling pathways that affect the microenvironment and the inflammatory response seem to play a central role in CRC. Indeed, some of these pathways directly regulate the stem/progenitor cell niche at the base of the crypt; it now appears that the survival and growth of neoplastic cells often relies upon their subverted engagement of these pathways. Spurned on by the use of gene manipulation technologies in the mouse, dissecting and recapitulating these complex molecular interactions between the tumor and its microenvironment in the gastrointestinal (GI) tract is a reality. In parallel, our ability to isolate and grow GI stem cells in vitro enables us, for the first time, to complement reductionist in vitro findings with complex in vivo observations. Surprisingly, data suggest that the large number of signaling pathways underpinning the reciprocal interaction between the neoplastic epithelium and its microenvironment converge on a small number of common transcription factors. Here, we review the separate and interactive roles of NFkappaB, Stat3, and Myb, transcription factors commonly overexpressed or excessively activated in CRC. They confer molecular links between inflammation, stroma, the stem cell niche, and neoplastic cell growth.
- Publisher
- WILEY-BLACKWELL
- Keywords
- cancer;colon;Lgr5;mouse models;Myb;NFκB;small intestine;Stat3;Wnt
- Research Division(s)
- Cell Signalling And Cell Death
- Publisher's Version
- https://doi.org/10.1111/j.1440-1746.2011.06883.x
- Terms of Use/Rights Notice
- © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Creation Date: 2014-01-20 09:37:36