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The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells
Altered glycolysis is a characteristic of many cancers, and can also be associated with changes in stem cell-like cancer (SCLC) cell populations. We therefore set out to directly examine the effect of glycolysis on SCLC cell phenotype, using a model where glycolysis is stably reduced by adapting the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955399/ https://www.ncbi.nlm.nih.gov/pubmed/29796188 http://dx.doi.org/10.18632/oncotarget.25299 |
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author | Banerjee, Arindam Arvinrad, Pardis Darley, Matthew Laversin, Stéphanie A. Parker, Rachel Rose-Zerilli, Matthew J.J. Townsend, Paul A. Cutress, Ramsey I. Beers, Stephen A. Houghton, Franchesca D. Birts, Charles N. Blaydes, Jeremy P. |
author_facet | Banerjee, Arindam Arvinrad, Pardis Darley, Matthew Laversin, Stéphanie A. Parker, Rachel Rose-Zerilli, Matthew J.J. Townsend, Paul A. Cutress, Ramsey I. Beers, Stephen A. Houghton, Franchesca D. Birts, Charles N. Blaydes, Jeremy P. |
author_sort | Banerjee, Arindam |
collection | PubMed |
description | Altered glycolysis is a characteristic of many cancers, and can also be associated with changes in stem cell-like cancer (SCLC) cell populations. We therefore set out to directly examine the effect of glycolysis on SCLC cell phenotype, using a model where glycolysis is stably reduced by adapting the cells to a sugar source other than glucose. Restricting glycolysis using this approach consistently resulted in cells with increased oncogenic potential; including an increase in SCLC cells, proliferation in 3D matrigel, invasiveness, chemoresistance, and altered global gene expression. Tumorigenicity in vivo was also markedly increased. SCLC cells exhibited increased dependence upon alternate metabolic pathways. They also became c-KIT dependent, indicating that their apparent state of maturation is regulated by glycolysis. Single-cell mRNA sequencing identified altered networks of metabolic-, stem- and signaling- gene expression within SCLC-enriched populations in response to glycolytic restriction. Therefore, reduced glycolysis, which may occur in niches within tumors where glucose availability is limiting, can promote tumor aggressiveness by increasing SCLC cell populations, but can also introduce novel, potentially exploitable, vulnerabilities in SCLC cells. |
format | Online Article Text |
id | pubmed-5955399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59553992018-05-24 The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells Banerjee, Arindam Arvinrad, Pardis Darley, Matthew Laversin, Stéphanie A. Parker, Rachel Rose-Zerilli, Matthew J.J. Townsend, Paul A. Cutress, Ramsey I. Beers, Stephen A. Houghton, Franchesca D. Birts, Charles N. Blaydes, Jeremy P. Oncotarget Research Paper Altered glycolysis is a characteristic of many cancers, and can also be associated with changes in stem cell-like cancer (SCLC) cell populations. We therefore set out to directly examine the effect of glycolysis on SCLC cell phenotype, using a model where glycolysis is stably reduced by adapting the cells to a sugar source other than glucose. Restricting glycolysis using this approach consistently resulted in cells with increased oncogenic potential; including an increase in SCLC cells, proliferation in 3D matrigel, invasiveness, chemoresistance, and altered global gene expression. Tumorigenicity in vivo was also markedly increased. SCLC cells exhibited increased dependence upon alternate metabolic pathways. They also became c-KIT dependent, indicating that their apparent state of maturation is regulated by glycolysis. Single-cell mRNA sequencing identified altered networks of metabolic-, stem- and signaling- gene expression within SCLC-enriched populations in response to glycolytic restriction. Therefore, reduced glycolysis, which may occur in niches within tumors where glucose availability is limiting, can promote tumor aggressiveness by increasing SCLC cell populations, but can also introduce novel, potentially exploitable, vulnerabilities in SCLC cells. Impact Journals LLC 2018-05-01 /pmc/articles/PMC5955399/ /pubmed/29796188 http://dx.doi.org/10.18632/oncotarget.25299 Text en Copyright: © 2018 Banerjee et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Banerjee, Arindam Arvinrad, Pardis Darley, Matthew Laversin, Stéphanie A. Parker, Rachel Rose-Zerilli, Matthew J.J. Townsend, Paul A. Cutress, Ramsey I. Beers, Stephen A. Houghton, Franchesca D. Birts, Charles N. Blaydes, Jeremy P. The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells |
title | The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells |
title_full | The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells |
title_fullStr | The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells |
title_full_unstemmed | The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells |
title_short | The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells |
title_sort | effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955399/ https://www.ncbi.nlm.nih.gov/pubmed/29796188 http://dx.doi.org/10.18632/oncotarget.25299 |
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