The APC network regulates the removal of mutated cells from colonic crypts

Song, J.-H., Huels, D. J., Ridgway, R. A., Sansom, O. J. , Kholodenko, B. N., Kolch, W. and Cho, K.-H. (2014) The APC network regulates the removal of mutated cells from colonic crypts. Cell Reports, 7(1), pp. 94-103. (doi: 10.1016/j.celrep.2014.02.043)

Abstract

Self-renewal is essential for multicellular organisms but carries the risk of somatic mutations that can lead to cancer, which is particularly critical for rapidly renewing tissues in a highly mutagenic environment such as the intestinal epithelium. Using computational modeling and in vivo experimentation, we have analyzed how adenomatous polyposis coli (APC) mutations and β-catenin aberrations affect the maintenance of mutant cells in colonic crypts. The increasing abundance of APC along the crypt axis forms a gradient of cellular adhesion that causes more proliferative cells to accelerate their movement toward the top of the crypt, where they are shed into the lumen. Thus, the normal crypt can efficiently eliminate β-catenin mutant cells, whereas APC mutations favor retention. Together, the molecular design of the APC/β-catenin signaling network integrates cell proliferation and migration dynamics to translate intracellular signal processing and protein gradients along the crypt into intercellular interactions and whole-crypt physiological or pathological behavior.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kolch, Prof Walter and Ridgway, Dr Rachel and Huels, Mr David and Sansom, Professor Owen
• Authors: Song, J.-H., Huels, D. J., Ridgway, R. A., Sansom, O. J., Kholodenko, B. N., Kolch, W., and Cho, K.-H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Reports
• Publisher: Elsevier
• ISSN: 2211-1247
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in Cell Reports 7(1):94-103
• Publisher Policy: Reproduced under a Creative Commons License