Altered propionate metabolism contributes to tumour progression and aggressiveness.
Nat Metab
; 4(4): 435-443, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35361954
ABSTRACT
The alteration of metabolic pathways is a critical strategy for cancer cells to attain the traits necessary for metastasis in disease progression. Here, we find that dysregulation of propionate metabolism produces a pro-aggressive signature in breast and lung cancer cells, increasing their metastatic potential. This occurs through the downregulation of methylmalonyl coenzyme A epimerase (MCEE), mediated by an extracellular signal-regulated kinase 2-driven transcription factor Sp1/early growth response protein 1 transcriptional switch driven by metastatic signalling at its promoter level. The loss of MCEE results in reduced propionate-driven anaplerotic flux and intracellular and intratumoral accumulation of methylmalonic acid, a by-product of propionate metabolism that promotes cancer cell invasiveness. Altogether, we present a previously uncharacterized dysregulation of propionate metabolism as an important contributor to cancer and a valuable potential target in the therapeutic treatment of metastatic carcinomas.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Propionatos
/
Neoplasias
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article