Mathematical modelling of phenotypic plasticity and conversion to a stem-cell state under hypoxia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-05

AUTHORS

Andrew Dhawan, Seyed Ali Madani Tonekaboni, Joseph H Taube, Stephen Hu, Nathalie Sphyris, Sendurai A Mani, Mohammad Kohandel

ABSTRACT

Hypoxia, or oxygen deficiency, is known to be associated with breast tumour progression, resistance to conventional therapies and poor clinical prognosis. The epithelial-mesenchymal transition (EMT) is a process that confers invasive and migratory capabilities as well as stem cell properties to carcinoma cells thus promoting metastatic progression. In this work, we examined the impact of hypoxia on EMT-associated cancer stem cell (CSC) properties, by culturing transformed human mammary epithelial cells under normoxic and hypoxic conditions, and applying in silico mathematical modelling to simulate the impact of hypoxia on the acquisition of CSC attributes and the transitions between differentiated and stem-like states. Our results indicate that both the heterogeneity and the plasticity of the transformed cell population are enhanced by exposure to hypoxia, resulting in a shift towards a more stem-like population with increased EMT features. Our findings are further reinforced by gene expression analyses demonstrating the upregulation of EMT-related genes, as well as genes associated with therapy resistance, in hypoxic cells compared to normoxic counterparts. In conclusion, we demonstrate that mathematical modelling can be used to simulate the role of hypoxia as a key contributor to the plasticity and heterogeneity of transformed human mammary epithelial cells. More... »

PAGES

18074

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep18074

DOI

http://dx.doi.org/10.1038/srep18074

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025627224

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26838463


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RDF/XML is a standard XML format for linked data.

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301 Metastasis Research Centre, The University of Texas MD Anderson Cancer Centre, Houston, Texas, United States of America.
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303 https://www.grid.ac/institutes/grid.249304.8 schema:alternateName Fields Institute for Research in Mathematical Sciences
304 schema:name Centre for Mathematical Medicine, Fields Institute for Research in Mathematical Sciences, Toronto, Ontario, Canada.
305 Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, Canada.
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307 https://www.grid.ac/institutes/grid.410356.5 schema:alternateName Queen's University
308 schema:name School of Medicine, Queen's University, Kingston, Ontario, Canada.
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310 https://www.grid.ac/institutes/grid.46078.3d schema:alternateName University of Waterloo
311 schema:name Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, Canada.
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