c-Src functionality controls self-renewal and glucose metabolism in MCF7 breast cancer stem cells.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
03
2020
accepted:
23
06
2020
entrez:
17
7
2020
pubmed:
17
7
2020
medline:
17
9
2020
Statut:
epublish
Résumé
Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells reduces tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of Breast Cancer Stem Cells (BCSCs) from MCF7 cells with inducible expression of SrcDN. Induction of SrcDN inhibited self-renewal, and stem-cell marker expression (Nanog, Oct3-4, ALDH1, CD44). Quantitative proteomic analyses of mammospheres from MCF7-Tet-On-SrcDN cells (data are available via ProteomeXchange with identifier PXD017789, project DOI: 10.6019/PXD017789) and subsequent GSEA showed that SrcDN expression inhibited glycolysis. Indeed, induction of SrcDN inhibited expression and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.
Identifiants
pubmed: 32673341
doi: 10.1371/journal.pone.0235850
pii: PONE-D-20-06055
pmc: PMC7365443
doi:
Substances chimiques
Hyaluronan Receptors
0
Nanog Homeobox Protein
0
Proteome
0
Aldehyde Dehydrogenase 1 Family
EC 1.2.1
src-Family Kinases
EC 2.7.10.2
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0235850Déclaration de conflit d'intérêts
The authors have declared that no competing of interests exist.
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