ArticleeLife2022
Metabolic requirement for GOT2 in pancreatic cancer depends on environmental context.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 111 citations in OpenAlex.
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.Redox biology · 2026Article
- Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death.Cell metabolism · 2026Article
- Oxaloacetate inhibition of succinate dehydrogenase: mechanism and physiological implications.American journal of physiology. Cell physiology · 2026Review
- Multi-Omics Analysis Reveals Differentially Expressed Proteins and Metabolites in Malignant Pleural Effusion.Thoracic cancer · 2026Article
- Adaptive plasticity of aspartate metabolism in succinate dehydrogenase-deficient cancer cells.bioRxiv : the preprint server for biology · 2026Article
- SHH drives gastric cancer-associated fibroblast activation via ACLY-dependent acetyl-CoA metabolism and histone acetylation.Discover oncology · 2026Article
- Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase.Nature metabolism · 2026Article
- GOT2-mediated suppression of CoQCommunications biology · 2026Article
- Glioblastoma cells utilize evolutionarily adapted cell metabolism to promote their malignant proliferation.Acta neuropathologica communications · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.bioRxiv : the preprint server for biology · 2026Article
- Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.Cancer & metabolism · 2026Article
- NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions.Nature metabolism · 2026Article
- A shift in the cellular redox state redirects aspartate for export under glucose deprivation.Cancer & metabolism · 2026Article
- GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.bioRxiv : the preprint server for biology · 2026Article
- Aspartate Transaminases Are Dispensable for Pancreatic Development and Pancreatic Cancer Progression.bioRxiv : the preprint server for biology · 2025Article
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- Context-Specific Metabolic Alterations in HPRT1 Knockout Cells Within a 3D Culture System.Cancer medicine · 2025Article
- WSSV-induced reversal of the malate-aspartate shuttle facilitates viral replication in shrimp hemocytes.Cell communication and signaling : CCS · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
31 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial glutamate-oxaloacetate transaminase 2 (GOT2) is part of the malate-aspartate shuttle, a mechanism by which cells transfer reducing equivalents from the cytosol to the mitochondria. GOT2 is a key component of mutant KRAS (KRAS*)-mediated rewiring of glutamine metabolism in pancreatic ductal adenocarcinoma (PDA). Here, we demonstrate that the loss of GOT2 disturbs redox homeostasis and halts proliferation of PDA cells in vitro. GOT2 knockdown (KD) in PDA cell lines in vitro induced NADH accumulation, decreased Asp and α-ketoglutarate (αKG) production, stalled glycolysis, disrupted the TCA cycle, and impaired proliferation. Oxidizing NADH through chemical or genetic means resolved the redox imbalance induced by GOT2 KD, permitting sustained proliferation. Despite a strong in vitro inhibitory phenotype, loss of GOT2 had no effect on tumor growth in xenograft PDA or autochthonous mouse models. We show that cancer-associated fibroblasts (CAFs), a major component of the pancreatic tumor microenvironment (TME), release the redox active metabolite pyruvate, and culturing GOT2 KD cells in CAF conditioned media (CM) rescued proliferation in vitro. Furthermore, blocking pyruvate import or pyruvate-to-lactate reduction prevented rescue of GOT2 KD in vitro by exogenous pyruvate or CAF CM. However, these interventions failed to sensitize xenografts to GOT2 KD in vivo, demonstrating the remarkable plasticity and differential metabolism deployed by PDA cells in vitro and in vivo. This emphasizes how the environmental context of distinct pre-clinical models impacts both cell-intrinsic metabolic rewiring and metabolic crosstalk with the TME.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.