The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer.
Cell Rep
; 14(4): 920-931, 2016 Feb 02.
Article
em En
| MEDLINE
| ID: mdl-26804918
ABSTRACT
Reprogramming of cellular metabolism plays a central role in fueling malignant transformation, and AMPK and the PGC-1α/ERRα axis are key regulators of this process. The intersection of gene-expression and binding-event datasets for breast cancer cells shows that activation of AMPK significantly increases the expression of PGC-1α/ERRα and promotes the binding of ERRα to its cognate sites. Unexpectedly, the data also reveal that ERRα, in concert with PGC-1α, negatively regulates the expression of several one-carbon metabolism genes, resulting in substantial perturbations in purine biosynthesis. This PGC-1α/ERRα-mediated repression of one-carbon metabolism promotes the sensitivity of breast cancer cells and tumors to the anti-folate drug methotrexate. These data implicate the PGC-1α/ERRα axis as a core regulatory node of folate cycle metabolism and further suggest that activators of AMPK could be used to modulate this pathway in cancer.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Neoplasias da Mama
/
Receptores de Estrogênio
/
Metotrexato
/
Antagonistas do Ácido Fólico
/
Antimetabólitos Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article