Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of
Breast cancer
Cell metabolism
Cell plasticity
Mitochondria
SDH
Journal
Cancer & metabolism
ISSN: 2049-3002
Titre abrégé: Cancer Metab
Pays: England
ID NLM: 101607582
Informations de publication
Date de publication:
2019
2019
Historique:
received:
11
12
2018
accepted:
04
04
2019
entrez:
6
6
2019
pubmed:
6
6
2019
medline:
6
6
2019
Statut:
epublish
Résumé
Epithelial to mesenchymal transition (EMT) is a well-characterized process of cell plasticity that may involve metabolic rewiring. In cancer, EMT is associated with malignant progression, tumor heterogeneity, and therapy resistance. In this study, we investigated the role of succinate dehydrogenase (SDH) as a potential key regulator of EMT. Associations between SDH subunits and EMT were explored in gene expression data from breast cancer patient cohorts, followed by in-depth studies of SDH suppression as a potential mediator of EMT in cultured cells. We found an overall inverse association between EMT and the SDH subunit C (SDHC) when analyzing gene expression in breast tumors. This was particularly evident in carcinomas of basal-like molecular subtype compared to non-basal-like tumors, and a low Our findings suggest that downregulation of SDHC promotes EMT and that this is accompanied by structural remodeling of the mitochondrial organelles. This may confer survival benefits upon exposure to hostile microenvironment including oxidative stress and hypoxia during cancer progression.
Sections du résumé
BACKGROUND
BACKGROUND
Epithelial to mesenchymal transition (EMT) is a well-characterized process of cell plasticity that may involve metabolic rewiring. In cancer, EMT is associated with malignant progression, tumor heterogeneity, and therapy resistance. In this study, we investigated the role of succinate dehydrogenase (SDH) as a potential key regulator of EMT.
METHODS
METHODS
Associations between SDH subunits and EMT were explored in gene expression data from breast cancer patient cohorts, followed by in-depth studies of SDH suppression as a potential mediator of EMT in cultured cells.
RESULTS
RESULTS
We found an overall inverse association between EMT and the SDH subunit C (SDHC) when analyzing gene expression in breast tumors. This was particularly evident in carcinomas of basal-like molecular subtype compared to non-basal-like tumors, and a low
CONCLUSIONS
CONCLUSIONS
Our findings suggest that downregulation of SDHC promotes EMT and that this is accompanied by structural remodeling of the mitochondrial organelles. This may confer survival benefits upon exposure to hostile microenvironment including oxidative stress and hypoxia during cancer progression.
Identifiants
pubmed: 31164982
doi: 10.1186/s40170-019-0197-8
pii: 197
pmc: PMC6544948
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
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