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Tytuł pozycji:

Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt.

Tytuł :
Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt.
Autorzy :
Romijn LB; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC, Australia.
Almet AA; Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, UK.; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, California, USA.; Department of Mathematics, University of California, Irvine, California, USA.
Tan CW; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Osborne JM; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC, Australia. .
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Źródło :
BMC bioinformatics [BMC Bioinformatics] 2020 Mar 03; Vol. 21 (1), pp. 95. Date of Electronic Publication: 2020 Mar 03.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Original Publication: [London] : BioMed Central, 2000-
MeSH Terms :
Models, Biological*
Colorectal Neoplasms/*metabolism
Cell Adhesion ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms/pathology ; Databases, Factual ; Humans ; Mutation ; Wnt Signaling Pathway
References :
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Contributed Indexing :
Keywords: Chaste; Colorectal cancer; Crypt; Multicellular modelling; SBML
Entry Date(s) :
Date Created: 20200305 Date Completed: 20200504 Latest Revision: 20200505
Update Code :
20210623
PubMed Central ID :
PMC7053074
DOI :
10.1186/s12859-020-3391-3
PMID :
32126976
Czasopismo naukowe
Background: Many cancers arise from mutations in cells within epithelial tissues. Mutations manifesting at the subcellular level influence the structure and function of the tissue resulting in cancer. Previous work has proposed how cell level properties can lead to mutant cell invasion, but has not incorporated detailed subcellular modelling RESULTS: We present a framework that allows the straightforward integration and simulation of SBML representations of subcellular dynamics within multiscale models of epithelial tissues. This allows us to investigate the effect of mutations in subcellular pathways on the migration of cells within the colorectal crypt. Using multiple models we find that mutations in APC, a key component in the Wnt signalling pathway, can bias neutral drift and can also cause downward invasion of mutant cells in the crypt.
Conclusions: Our framework allows us to investigate how subcellular mutations, i.e. knockouts and knockdowns, affect cell-level properties and the resultant migration of cells within epithelial tissues. In the context of the colorectal crypt, we see that mutations in APC can lead directly to mutant cell invasion.
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