UCP1 regulates ALDH-positive breast cancer stem cells through releasing the suppression of Snail on FBP1.
Cell Biol Toxicol
; 37(2): 277-291, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-32472219
ABSTRACT
Uncoupling protein 1 (UCP1) has been implicated in ameliorating metabolic related disorders, of which most symptoms are risk factors for breast cancer. Here, we found that UCP1 was obviously downregulated in basal-like breast cancer (BLBC) and was positively correlated with improved survival. However, the underlying regulatory mechanisms remain largely unknown. Our studies showed that UCP1 inhibited tumor progression via suppressing aldehyde dehydrogenase (ALDH)-positive breast cancer stem cell (BCSC) population in BLBC. Furthermore, we found that UCP1 induced the upregulation of fructose bisphosphatase 1 (FBP1) which was previously blocked by Snail overexpression, and UCP1 decreased ALDH-positive BCSCs via FBP1-dependent metabolic rewiring, which could be reversed by Snail overexpression. In addition, breast cancer cells co-cultured with UCP1-deficient adipocytes had increased proportion of ALDH-positive BCSCs, indicating a potential protection role of UCP1 in tumor microenvironment. These results suggested that UCP1 suppressed BCSCs through inhibiting Snail-mediated repression of FBP1, and that upregulation of UCP1 might be a previously undescribed therapeutic strategy for combating breast cancer. Graphical abstract.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Aldeído Desidrogenase
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Proteína Desacopladora 1
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Fatores de Transcrição da Família Snail
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cell Biol Toxicol
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article