ArticleCancer & metabolism2020
Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy.
Article in Cancer & metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.Nature communications · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.Redox biology · 2026Article
- Gene overexpression reduces inhibitory metabolites to enhance CHO cell growth and IgG1 production.NPJ systems biology and applications · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.bioRxiv : the preprint server for biology · 2026Article
- NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions.Nature metabolism · 2026Article
- Aspartate availability drives differential engagement of the malate-aspartate shuttle.Molecular cell · 2026Article
- GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pan-cancer molecular signatures connecting aspartate transaminase to cancer prognosis, metabolic and immune signatures.Frontiers in oncology · 2026Article
- Adaptive nuclear GTP synthesis promotes glioblastoma treatment resistance and is a targetable vulnerability in patients.medRxiv : the preprint server for health sciences · 2025Article
- Autophagy Upregulation in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma Uncovers a Novel Therapeutic Target.Research square · 2025Article
- Genome-scale modeling identifies dynamic metabolic vulnerabilities during the epithelial to mesenchymal transition.Communications biology · 2024Article
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Glutamate oxaloacetate transaminase 1 is dispensable in macrophage differentiation and anti-pathogen response.Communications biology · 2024Article
- SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1.Cellular and molecular life sciences : CMLS · 2024Article
- The role of GOT1 in cancer metabolism.Frontiers in oncology · 2024Review
- Glucose-6-phosphate dehydrogenase deficiency accelerates pancreatic acinar-to-ductal metaplasia.bioRxiv : the preprint server for biology · 2023Article
- Article
- Review
- Integrative analysis of plasma metabolomics and proteomics reveals the metabolic landscape of breast cancer.Cancer & metabolism · 2022Article
- Unraveling and targeting RAS-driven metabolic signaling for therapeutic gain.Advances in cancer research · 2022Review
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundMetabolic programs in cancer cells are influenced by genotype and the tissue of origin. We have previously shown that central carbon metabolism is rewired in pancreatic ductal adenocarcinoma (PDA) to support proliferation through a glutamate oxaloacetate transaminase 1 (GOT1)-dependent pathway.
methodsWe utilized a doxycycline-inducible shRNA-mediated strategy to knockdown GOT1 in PDA and colorectal cancer (CRC) cell lines and tumor models of similar genotype. These cells were analyzed for the ability to form colonies and tumors to test if tissue type impacted GOT1 dependence. Additionally, the ability of GOT1 to impact the response to chemo- and radiotherapy was assessed. Mechanistically, the associated specimens were examined using a combination of steady-state and stable isotope tracing metabolomics strategies and computational modeling. Statistics were calculated using GraphPad Prism 7. One-way ANOVA was performed for experiments comparing multiple groups with one changing variable. Student's
resultsWhile PDA exhibits profound growth inhibition upon GOT1 knockdown, we found CRC to be insensitive. In PDA, but not CRC, GOT1 inhibition disrupted glycolysis, nucleotide metabolism, and redox homeostasis. These insights were leveraged in PDA, where we demonstrate that radiotherapy potently enhanced the effect of GOT1 inhibition on tumor growth.
conclusionsTaken together, these results illustrate the role of tissue type in dictating metabolic dependencies and provide new insights for targeting metabolism to treat PDA.
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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.