ArticleCell reports2021
Metabolic compensation activates pro-survival mTORC1 signaling upon 3-phosphoglycerate dehydrogenase inhibition in osteosarcoma.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 46 citations in OpenAlex.
- PSAT1 inhibits mTORC1 activation by preventing Rag heterodimer formation in lung adenocarcinoma.Autophagy · 2026Article
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Metabolic reprogramming-related drug resistance in osteosarcoma: from molecular mechanisms to therapeutic translation.Frontiers in molecular biosciences · 2026Review
- Metabolic-immune crosstalk in osteosarcoma: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Single-cell RNA and bulk sequencing analysis reveals that formononetin inhibits GTSF1 to exert anti-osteosarcoma effects.APL bioengineering · 2025Article
- Molecular and Glycosylation Pathways in Osteosarcoma: Tumor Microenvironment and Emerging Strategies Toward Personalized Oncology.Current issues in molecular biology · 2025Review
- PHGDH inhibition and FOXO3 modulation drives PUMA-dependent apoptosis in osteosarcoma.Cell death & disease · 2025Article
- Osteosarcoma immunometabolism: emerging mechanisms and clinical implications.Frontiers in immunology · 2025Review
- E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.Cancer research · 2024Article
- Tracing the Diverse Paths of One-Carbon Metabolism in Cancer and Beyond.Cold Spring Harbor perspectives in medicine · 2024Review
- Characterization of the gut microbiota and fecal metabolome in the osteosarcoma mouse model.Aging · 2024Article
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- Advances in prognostic models for osteosarcoma risk.Heliyon · 2024Review
- Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer.Cancer discovery · 2024Article
- A pancreatic cancer organoid platform identifies an inhibitor specific to mutant KRAS.Cell stem cell · 2024Article
- Serine metabolism in macrophage polarization.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth.Nature communications · 2023Article
- Metabolic reprogramming in osteosarcoma.Pediatric discovery · 2023Review
- Amino Acid Metabolism in Bone Metastatic Disease.Current osteoporosis reports · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Osteosarcoma is the most common pediatric and adult primary malignant bone cancer. Curative regimens target the folate pathway, downstream of serine metabolism, with high-dose methotrexate. Here, the rate-limiting enzyme in the biosynthesis of serine from glucose, 3-phosphoglycerate dehydrogenase (PHGDH), is examined, and an inverse correlation between PHGDH expression and relapse-free and overall survival in osteosarcoma patients is found. PHGDH inhibition in osteosarcoma cell lines attenuated cellular proliferation without causing cell death, prompting a robust metabolic analysis to characterize pro-survival compensation. Using metabolomic and lipidomic profiling, cellular response to PHGDH inhibition is identified as accumulation of unsaturated lipids, branched chain amino acids, and methionine cycle intermediates, leading to activation of pro-survival mammalian target of rapamycin complex 1 (mTORC1) signaling. Increased mTORC1 activation sensitizes cells to mTORC1 pathway inhibition, resulting in significant, synergistic cell death in vitro and in vivo. Identifying a therapeutic combination for PHGDH-high cancers offers preclinical justification for a dual metabolism-based combination therapy for osteosarcoma.
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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.