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

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Title: The APC network regulates the removal of mutated cells from colonic crypts
Authors: Song, Je-Hoon
Huels, David J.
Ridgway, Rachel A.
Kholodenko, Boris N.
Kolch, Walter
et al.
Permanent link: http://hdl.handle.net/10197/9789
Date: 10-Apr-2014
Online since: 2019-04-03T10:15:08Z
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.
Funding Details: European Commission - Seventh Framework Programme (FP7)
European Research Council
Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Journal: Cell Reports
Volume: 7
Issue: 1
Start page: 94
End page: 103
Copyright (published version): 2014 the Authors
Keywords: APCComputational modelingIn vivo experimentationAdenomatous polyposis coli mutationsβ-cateninColonic crypts
DOI: 10.1016/j.celrep.2014.02.043
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

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