The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells - ePrints Soton
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 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.
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Arvinrad, Pardis
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Darley, Matthew
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Laversin, Stephanie A
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Birts, Charles
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Banerjee, Arindam, Arvinrad, Pardis, Darley, Matthew, Laversin, Stephanie A, Parker, Rachel, Rose-Zerilli, Matthew, Townsend, Paul A., Cutress, Ramsey, Beers, Stephen, Houghton, Franchesca D, Birts, Charles and Blaydes, Jeremy (2018) The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells. Oncotarget, 9 (33), 23274-23288. (doi:10.18632/oncotarget.25299).
25299-1003227-5-PB - Version of Record
PURE UUID: 4b71c7d2-dd41-4607-96b0-72d625bdcb89
ORCID for Arindam Banerjee: orcid.org/0000-0003-2292-4936
ORCID for Charles Birts: orcid.org/0000-0002-0368-8766
Author: Arindam Banerjee
Author: Pardis Arvinrad
Author: Matthew Darley
Author: Stephanie A Laversin
Author: Charles Birts