The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells.
Cell Death Dis
; 12(4): 408, 2021 04 15.
Article
en En
| MEDLINE
| ID: mdl-33859186
ABSTRACT
One of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes. Phosphofructokinase (PFKM), one of the most important regulatory enzymes of glycolysis, was S-nitrosylated by nitric oxide synthase NOS1 at Cys351. S-nitrosylation at Cys351 stabilized the tetramer of PFKM, leading to resist negative feedback of downstream metabolic intermediates. The PFKM-C351S mutation decreased the proliferation rate of cultured cancer cells, and reduced tumor growth and metastasis in the mouse xenograft model. These findings indicated that S-nitrosylation at Cys351 of PFKM by NOS1 contributes to the metabolic reprogramming of ovarian cancer cells, highlighting a critical role of endogenous nitrogen oxide on metabolism regulations in tumor progression.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Fosfofructoquinasa-1 Tipo Muscular
/
Carcinoma Epitelial de Ovario
/
Glucólisis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2021
Tipo del documento:
Article
País de afiliación:
China