ArticleNature metabolism2022
Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 67 citations in OpenAlex.
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- Cell Penetrating Thyclotides Facilitate Efficient Delivery of Bioactive Peptides into Cells.bioRxiv : the preprint server for biology · 2026Article
- A novel EGR1-driven GLUL/mTOR axis regulates macropinocytosis-mediated crosstalk in pancreatic stellate cell-cancer metastasis.Journal of translational medicine · 2026Article
- Microplastics as Vectors Influencing Oxidative Stress, Inflammation, and Endocrine Function During Early Development.International journal of molecular sciences · 2026Review
- Adaptive plasticity of aspartate metabolism in succinate dehydrogenase-deficient cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells.Tumour virus research · 2026Article
- Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase.Nature metabolism · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.bioRxiv : the preprint server for biology · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- A shift in the cellular redox state redirects aspartate for export under glucose deprivation.Cancer & metabolism · 2026Article
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- Impact of diabetes mellitus on treatment efficacy in patients with advanced pancreatic cancer: the Italian, multicenter, observational PANCAKE study.ESMO gastrointestinal oncology · 2026Article
- GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated analysis of glutamine metabolism and immune microenvironment identifies GOT2 as a prognostic gene in head and neck squamous cell carcinoma.Discover oncology · 2026Article
- Mitochondrial complex I in focus: mechanisms and therapeutic strategies of urinary system diseases.Frontiers in physiology · 2026Review
- Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma.Nature communications · 2025Article
- Aspartate Transaminases Are Dispensable for Pancreatic Development and Pancreatic Cancer Progression.bioRxiv : the preprint server for biology · 2025Article
- Hypoxia response in glioblastoma cells: effect of trehalose on macropinocytosis, autophagy and cell survival.Biochemistry and biophysics reports · 2025Article
- Macropinocytosis fuels osteoclast differentiation in bone-related diseases.Journal of orthopaedic translation · 2025Article
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17 authors at 5 institutions in 1 country.
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Abstract
Stress-adaptive mechanisms enable tumour cells to overcome metabolic constraints under nutrient and oxygen shortage. Aspartate is an endogenous metabolic limitation under hypoxic conditions, but the nature of the adaptive mechanisms that contribute to aspartate availability and hypoxic tumour growth are poorly understood. Here we identify GOT2-catalysed mitochondrial aspartate synthesis as an essential metabolic dependency for the proliferation of pancreatic tumour cells under hypoxic culture conditions. In contrast, GOT2-catalysed aspartate synthesis is dispensable for pancreatic tumour formation in vivo. The dependence of pancreatic tumour cells on aspartate synthesis is bypassed in part by a hypoxia-induced potentiation of extracellular protein scavenging via macropinocytosis. This effect is mutant KRAS dependent, and is mediated by hypoxia-inducible factor 1 (HIF1A) and its canonical target carbonic anhydrase-9 (CA9). Our findings reveal high plasticity of aspartate metabolism and define an adaptive regulatory role for macropinocytosis by which mutant KRAS tumours can overcome nutrient deprivation under hypoxic conditions.
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