ArticleCancer & metabolism2020
PHGDH supports liver ceramide synthesis and sustains lipid homeostasis.
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 24 papers.
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Who cites it
24 citing papers in PubMed.
- Serine Starvation Modulates mRNA Splicing through Translational Inhibition of SRSF Proteins.Cancer research · 2026Article
- Metagenomic and Metabolomic Correlates of Immunotherapy Response in Non-Small Cell Lung Cancer.Research square · 2026Article
- Stable bioreactor control reveals acidic pH-driven metabolic reprogramming and mitochondrial dysfunction in human lymphoblastoid cells.Communications biology · 2026Article
- PHGDH mediated serine biosynthesis metabolism suppresses vascular calcification.Biology direct · 2026Article
- PHGDH is a targetable driver of PDAC progression.bioRxiv : the preprint server for biology · 2026Article
- Integrating omics and functional data via representation learning to prioritize candidate genes for pleiotropic effect in dairy sheep.PNAS nexus · 2025Article
- Methylation risk score of C-reactive protein associates sleep health with related health outcomes.Communications biology · 2025Article
- Nonessential amino acid is not nonessential in geriatric patients: implications for maxillofacial wound healing and bone repair.Maxillofacial plastic and reconstructive surgery · 2025Review
- PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability.Cancer research · 2025Article
- Supplementation of Oocytes by Microinjection with Extra Copies of mtDNA Alters Metabolite Profiles and Interactions with Expressed Genes in a Tissue-Specific Manner.Biomolecules · 2024Article
- E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.Cancer research · 2024Article
- Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.Nature communications · 2024Article
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability.bioRxiv : the preprint server for biology · 2024Article
- Investigating the Mechanism of Low-Salinity Environmental Adaptation inAnimals : an open access journal from MDPI · 2023Article
- Serine Metabolic Reprogramming in Tumorigenesis, Tumor Immunity, and Clinical Treatment.Advances in nutrition (Bethesda, Md.) · 2023Review
- Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma.Frontiers in neurology · 2022Article
- TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation.Cardiology research and practice · 2022Article
- Hepatocyte-SpecificNutrients · 2021Article
- DNA Methylation and Blood Pressure Phenotypes: A Review of the Literature.American journal of hypertension · 2021Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundd-3-phosphoglycerate dehydrogenase (PHGDH), which encodes the first enzyme in serine biosynthesis, is overexpressed in human cancers and has been proposed as a drug target. However, whether PHGDH is critical for the proliferation or homeostasis of tissues following the postnatal period is unknown.
methodsTo study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA under the control of a doxycycline-inducible promoter. With this model, PHGDH depletion can be globally induced in adult animals, while sparing the brain due to poor doxycycline delivery.
resultsWe found that PHGDH depletion is well tolerated, and no overt phenotypes were observed in multiple highly proliferative cell compartments. Further, despite detectable knockdown and impaired serine synthesis, liver and pancreatic functions were normal. Interestingly, diminished PHGDH expression reduced liver serine and ceramide levels without increasing the levels of deoxysphingolipids. Further, liver triacylglycerol profiles were altered, with an accumulation of longer chain, polyunsaturated tails upon PHGDH knockdown.
conclusionsThese results suggest that dietary serine is adequate to support the function of healthy, adult murine tissues, but PHGDH-derived serine supports liver ceramide synthesis and sustains general lipid homeostasis.
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