ArticleProceedings of the National Academy of Sciences of the United States of America2023
PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- Metabolic remodeling by circular RNAs in gastric tumorigenesis: From mechanisms to biomarker discovery (Review).International journal of oncology · 2026Review
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- Patient-Derived Organoids from Multiple Sites of a Single Tumor Recapitulates Intratumoral Heterogeneity in Patients with Gastric Cancer.Gut and liver · 2026Article
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Metabolic Reprogramming in Gastric Cancer Immunity Mechanisms and Therapeutic Implications.Oncology research · 2026Review
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
- Review
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer.Cell death discovery · 2025Article
- Article
- PKA-Mediated Phosphorylation of SFRP4 Promotes Wnt/β-Catenin Activation and Cancer Stemness in Gastric Cancer.International journal of molecular sciences · 2025Article
- Advances in the Study of Metabolic Reprogramming in Gastric Cancer.Cancer medicine · 2025Review
- Serine metabolism in tumor progression and immunotherapy.Discover oncology · 2025Review
- Garlic-Derived Exosome-Like Nanovesicles: A Promising Natural Nanotherapy for Periodontitis via PHGDH/PI3K/AKT-Mediated Metabolic and Inflammatory Regulation.International journal of nanomedicine · 2025Article
- The role and research progress of serine metabolism in tumor cells.Frontiers in oncology · 2025Review
- Targeting amino acid metabolism to inhibit gastric cancer progression and promote anti-tumor immunity: a review.Frontiers in immunology · 2025Review
- Article
- Overcoming Cancer Persister Cells by Stabilizing the ATF4 Promoter G-quadruplex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients.
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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.