Glutamine is a substrate for glycosylation and CA19-9 biosynthesis through hexosamine biosynthetic pathway in pancreatic cancer.
Discov Oncol
; 14(1): 20, 2023 Feb 17.
Article
en En
| MEDLINE
| ID: mdl-36797531
ABSTRACT
BACKGROUND:
Carbohydrate antigen 19-9 (CA19-9) is the most widely used biomarker for pancreatic cancer. Since CA19-9 closely correlates with patient outcome and tumor stage in pancreatic cancer, the deciphering of CA19-9 biosynthesis provides a potential clue for treatment.METHODS:
Concentration of amino acids was detected by ultrahigh-performance liquid chromatography tandem mass spectrometry. Metabolic flux of glutamine was examined by isotope tracing untargeted metabolomics. Label-free quantitative N-glycosylation proteomics was used to examine N-glycosylation alterations.RESULTS:
Among all amino acids, glutamine was higher in CA19-9-high pancreatic cancers (> 37 U/mL, 66 cases) than in CA19-9-normal clinical specimens (≤ 37 U/mL, 37 cases). The glutamine concentration in clinical specimens was positively correlated with liver metastasis or lymphovascular invasion. Glutamine blockade using diazooxonorleucine suppressed pancreatic cancer growth and intraperitoneal and lymphatic metastasis. Glutamine promotes O-GlcNAcylation, protein glycosylation, and CA19-9 biosynthesis through the hexosamine biosynthetic pathway. UDP-N-acetylglucosamine (UDP-GlcNAc) levels correlated with the glutamine influx through hexosamine biosynthetic pathway and supported CA19-9 biosynthesis.CONCLUSIONS:
Glutamine is a substrate for CA19-9 biosynthesis in pancreatic cancer. Glutamine blockade may be a potential therapeutic strategy for pancreatic cancer.
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Base de datos:
MEDLINE
Idioma:
En
Revista:
Discov Oncol
Año:
2023
Tipo del documento:
Article
País de afiliación:
China