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The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells

The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells
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.
1949-2553
23274-23288
Banerjee, Arindam
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Arvinrad, Pardis
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Darley, Matthew
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Laversin, Stephanie A
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Parker, Rachel
ca68b9e6-b3d4-4246-845f-4636068d479f
Rose-Zerilli, Matthew
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Townsend, Paul A.
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Cutress, Ramsey
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Beers, Stephen
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Houghton, Franchesca
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Birts, Charles
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Blaydes, Jeremy
e957f999-fd91-4f77-ad62-5b4ef069b15b
Banerjee, Arindam
7e1217f4-949a-4851-be1a-c597e31a38b9
Arvinrad, Pardis
91ce8f9a-bfc1-4b56-92ac-f8725cddffe5
Darley, Matthew
7be23780-a781-4dd4-a74c-f5affbb79521
Laversin, Stephanie A
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Parker, Rachel
ca68b9e6-b3d4-4246-845f-4636068d479f
Rose-Zerilli, Matthew
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Cutress, Ramsey
68ae4f86-e8cf-411f-a335-cdba51797406
Beers, Stephen
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Houghton, Franchesca
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Birts, Charles
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Blaydes, Jeremy
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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, 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).

Record type: Article

Abstract

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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Accepted/In Press date: 8 April 2018
e-pub ahead of print date: 1 May 2018
Published date: 2018

Identifiers

Local EPrints ID: 419831
URI: https://eprints.soton.ac.uk/id/eprint/419831
ISSN: 1949-2553
PURE UUID: 4b71c7d2-dd41-4607-96b0-72d625bdcb89
ORCID for Arindam Banerjee: ORCID iD orcid.org/0000-0003-2292-4936
ORCID for Matthew Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for Charles Birts: ORCID iD orcid.org/0000-0002-0368-8766
ORCID for Jeremy Blaydes: ORCID iD orcid.org/0000-0001-8525-0209

Catalogue record

Date deposited: 23 Apr 2018 16:30
Last modified: 15 Aug 2019 04:15

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Contributors

Author: Pardis Arvinrad
Author: Matthew Darley
Author: Stephanie A Laversin
Author: Rachel Parker
Author: Paul A. Townsend
Author: Ramsey Cutress
Author: Stephen Beers
Author: Charles Birts ORCID iD
Author: Jeremy Blaydes ORCID iD

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