ArticleThe Journal of clinical investigation2021
Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 92 citations in OpenAlex.
- Metabolites and cancer metastasis.Oncogene · 2026Review
- LC-MS/MS-based clinical value exploration of the methionine cycle in luminal breast cancer.Oncology letters · 2026Article
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- α-ketoglutarate accumulation orchestrates immunosuppressive metabolic remodeling to drive cetuximab resistance in metastatic colorectal cancer.Cell death & disease · 2026Article
- Homeobox A10 in gastrointestinal malignancies: unraveling metastatic mechanisms and novel therapeutic opportunities.Cancer metastasis reviews · 2026Review
- L-serine at the crossroads of microbiota, intestinal health, and disorders.Communications biology · 2026Review
- Integrative analysis and functional validation identified palmitoylated PHGDH as a therapeutic target for colon adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Arginine dependency in omental metastasis of epithelial ovarian cancer reveals a therapeutic vulnerability.Cell death & disease · 2026Article
- Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026Review
- Macrophage Metabolic Reprogramming-Related Osteoimmunity in Osteoporosis.Calcified tissue international · 2026Review
- The Senescence-SASP Landscape in Colon Adenocarcinoma: Prognostic and Therapeutic Implications.Current issues in molecular biology · 2026Article
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- O-GlcNAcylation of DDB1 at Ser-764 by OGT promotes cancer cell stemness in colorectal cancer through increased polyubiquitination of p53.Scientific reports · 2025Article
- Oral Administrations of Short-Chain Fatty Acids or Probiotics Extend the Survival Times and Mitigate the Neuropathological Damages in the Scrapie-Infected Hamsters.Molecular neurobiology · 2025Article
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Methionine induced placental angiogenesis through activating WNT3A/CTNNB1-PIGF-VEGFR1 pathway.Cell communication and signaling : CCS · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.Current issues in molecular biology · 2025Review
- Bone Marrow Adipoq-lineage Progenitors: an Emerging Osteoclast Niche Cell Population.Current osteoporosis reports · 2025Review
- NSUN2 promotes colorectal cancer progression by stabilizing PHGDH mRNA to promote serine metabolism reprogramming.Cancer & metabolism · 2025Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although serine metabolism plays a crucial role in the proliferation and survival of tumor cells, how it supports tumor cell migration remains poorly understood. Phosphoglycerate dehydrogenase (PHGDH) catalyzes the oxidation of 3-phosphoglycerate to 3-phosphonooxypyruvate, the first committed step in de novo serine biosynthesis. Here we show that PHGDH was monoubiquitinated by cullin 4A-based E3 ligase complex at lysine 146 in colorectal cancer (CRC) cells, which enhanced PHGDH activity by recruiting a chaperone protein, DnaJ homolog subfamily A member 1, to promote its tetrameric formation, thereby increasing the levels of serine, glycine, and S-adenosylmethionine (SAM). Increased levels of SAM upregulated the expression of cell adhesion genes (laminin subunit gamma 2 and cysteine rich angiogenic inducer 61) by initiating SET domain containing 1A-mediated trimethylation of histone H3K4, thereby promoting tumor cell migration and CRC metastasis. Intriguingly, SAM levels in tumors or blood samples correlated with the metastatic recurrence of patients with CRC. Our finding not only reveals a potentially new role and mechanism of SAM-promoted tumor metastasis but also demonstrates a regulatory mechanism of PHGDH activity by monoubiquitination.
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