All metabolites were detected over a mass range of 25000-200 m/z using the Exactive Orbitrap mass spectrometer (Thermo Scientific, Waltham, MA, USA) with electrospray (ESI) ionization and polarity switching.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - hilic"],"chromatography_protocol":["Samples (5mL) were analyzed using an Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific) coupled with an Accela HPLC system equipped with a ZIC-pHILIC column (150 mm x 2.1 mm, 5 mm, Merck KGaA) and a guard column (20 mm x 2.1 mm). Chromatographic separation was achieved using a 15-minute gradient from 80% to 20% acetonitrile (mobile phase: 20% 10 mM ammonium carbonate, pH 9.4). The column was maintained at 45 °C and a flow rate of 200 mL/min.
"],"publication":["Crosstalk between S-nitrosylation and glycation defines a novel metabolic vulnerability in liver and renal cancers."],"submitter_affiliation":["danish cancer institute"],"submitter_name":["chiara Pecorari"],"organism_part":["Harvest of Product from Whole Cell Lysate"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Briefly, cell monolayers were washed twice with ice-cold PBS, and metabolites were extracted using 1000 mL of ice-cold extraction buffer (methanol:acetonitrile:water, 5:3:3 v/v/v). Extracts were incubated at 4°C for 10 min.
"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS15003"],"author":["chiara Pecorari. danish cancer institute. chp@cancer.dk."],"data_transformation_protocol":["Raw LC-MS data files were processed for peak detection, alignment, integration and normalization. Peak intensities were exported as a metabolite abundance table and used for metabolite assignment.
"],"study_factor":["Biological replicates","Time point","Genotype"],"submitter_email":["chp@cancer.dk"],"sample_collection_protocol":["Briefly, cell monolayers were washed twice with ice-cold PBS, and metabolites were extracted using 1000 mL of ice-cold extraction buffer (methanol:acetonitrile:water, 5:3:3 v/v/v).
"],"omics_type":["Metabolomics"],"study_design":["Metabolomics","Waters ACQUITY UPLC H-Class System","renal carcinoma","targeted analysis","siAKR1A1","Homo sapiens","Harvest of Product from Whole Cell Lysate","control","LC-MS","siAKR1A1 tracing 6h","Thermo Scientific Q Exactive HF","hepatocellular carcinoma","control tracing 6h"],"curator_keywords":["Metabolomics","renal carcinoma","Waters ACQUITY UPLC H-Class System","targeted analysis","siAKR1A1","Homo sapiens","Harvest of Product from Whole Cell Lysate","control","LC-MS","siAKR1A1 tracing 6h","Thermo Scientific Q Exactive HF","hepatocellular carcinoma","control tracing 6h"],"mass_spectrometry_protocol":["Mass spectrometry was performed in full-scan mode with polarity switching and a resolution of 25,000 at 200 m/z allowing for simultaneous determination of positive and negative ions in a 23 min-analysis. Lock masses ensured mass accuracy <5 ppm for all metabolites. Data acquisition was performed using Thermo LCquan 2.7 (Thermo Fisher Scientific). Metabolite abundance was normalized to protein content determined by the Lowry assay.
"],"additional_accession":[]},"is_claimable":false,"name":"Crosstalk between S-nitrosylation and glycation defines a novel metabolic vulnerability in liver and renal cancers","description":"Metabolic reprogramming is a defining feature of cancer; however, how it contributes to therapeutic resistance remains incompletely understood. Here we show that loss of aldo-ketoreductase 1A1 (AKR1A1) in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) disrupts terminal glycolytic flux and lactate production through S-nitrosylation-mediated inhibition of pyruvate kinase, resulting in the accumulation of methylglyoxal (MGO). In multiple AKR1A1-deficient models, but not in those endogenously expressing the C423/424A mutant of pyruvate kinase M2, elevated MGO triggers autophagic degradation of Kelch-like ECH-associated protein 1, leading to Nuclear factor erythroid 2-Related Factor 2 (NRF2) activation and transcriptional reprogramming. This NRF2-driven response enhances chemoresistance and promotes tumor cell migration, two hallmarks of aggressive cancer. Therapeutically, we demonstrate that pharmacological inhibition of the glyoxalase system—the major pathway for MGO detoxification—restores drug sensitivity in patient-derived cells and xenograft models, revealing a context-dependent metabolic vulnerability in AKR1A1 loss conditions. These findings identify AKR1A1 as a metabolic tumor suppressor and uncover crosstalk between S-nitrosylation and glycation as a key regulatory axis linking metabolic reprogramming to NRF2-driven therapy resistance, offering glyoxalase inhibition as a potential precision treatment strategy for RCC and HCC.
","dates":{"publication":"2026-07-10","submission":"2026-07-10"},"accession":"MTBLS15003","cross_references":{}}