Ontology highlight
ABSTRACT: Metabolic reprogramming is a hallmark of cancer and is crucial for cancer progression, making it an attractive therapeutic target. Understanding the role of metabolic reprogramming in cancer initiation could help identify prevention strategies. To address this, we investigated metabolism during acinar-to-ductal metaplasia (ADM), the first step of pancreatic carcinogenesis. Glycolytic markers were elevated in ADM lesions compared to normal tissue from human samples. Comprehensive metabolic assessment in three mouse models with pancreas-specific activation of KRAS, PI3K or MEK1 using Seahorse measurements, NMR metabolome analysis, mass spectrometry, isotope tracing and RNA-seq analysis revealed a switch from oxidative phosphorylation to glycolysis in ADM. Blocking the metabolic switch attenuated ADM formation. Furthermore, mitochondrial metabolism was required for de novo synthesis of serine and glutathione but not for ATP production. MYC mediated the increase in GSH intermediates in ADM, and inhibition of GSH synthesis suppressed ADM development. This study thus identifies metabolic changes and vulnerabilities in the early stages of pancreatic carcinogenesis.
INSTRUMENT(S): Liquid Chromatography MS - alternating - hilic
SUBMITTER: Werner Schmitz
PROVIDER: MTBLS9772 | MetaboLights | 2024-05-31
REPOSITORIES: MetaboLights
Action | DRS | |||
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MTBLS9772 | Other | |||
FILES | Other | |||
a_MTBLS9772_LC-MS_alternating_hilic_metabolite_profiling.txt | Txt | |||
i_Investigation.txt | Txt | |||
m_MTBLS9772_LC-MS_alternating_hilic_metabolite_profiling_v2_maf.tsv | Tabular |
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