Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet.
FEBS J
; 291(8): 1699-1718, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38245817
ABSTRACT
Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to the influence of obesity and diabetes mellitus on disease initiation and progression. In this study, we investigated the pathogenesis of pancreatic cancer in mice subjected to a high-fat diet (HFD) and observed an increase in citric acid expenditure. Notably, citrate treatment demonstrates significant efficacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo. Our investigations revealed that citrate achieved these effects by releasing secreted protein acidic and rich in cysteine (SPARC) proteins, repolarizing M2 macrophages into M1 macrophages, and facilitating tumor cell apoptosis. Overall, our research highlights the critical role of citric acid as a pivotal metabolite in the intricate relationship between obesity and pancreatic cancer. Furthermore, we uncovered the significant metabolic and immune checkpoint function of SPARC in pancreatic cancer, suggesting its potential as both a biomarker and therapeutic target in treating this patient population.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Osteonectina
Idioma:
En
Revista:
FEBS J
Asunto de la revista:
BIOQUIMICA
Año:
2024
Tipo del documento:
Article