ArticleProceedings of the National Academy of Sciences of the United States of America2023
The PLOD2/succinate axis regulates the epithelial-mesenchymal plasticity and cancer cell stemness.
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 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Lactate-induced H3K4me3 histone mark promotes PLOD1-driven prostate cancer invasion.Cell death & disease · 2026Article
- Bottom-Up Programming of Cell States in Cancer Organoids with Defined Synthetic Adhesion Cues.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- A novel microprotein MUCP1 promotes colorectal cancer metabolic reprogramming by regulating mitochondrial succinate transport.Neoplasia (New York, N.Y.) · 2026Article
- PLOD2 promotes proliferation, migration and invasion of colorectal cancer cells via PI3K-AKT-GSK3β signaling pathway.Scientific reports · 2026Article
- Epigenetic co-regulator HCF-1 promotes lung cancer via O-GlcNAcylation-dependent pathways.Molecular therapy. Oncology · 2025Article
- TET-mediated 5hmC in breast cancer: mechanism and clinical potential.Epigenetics · 2025Review
- Collagen dynamics in the breast cancer tumor microenvironment and therapeutic perspectives.Discover oncology · 2025Review
- Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules.ACS central science · 2025Article
- Role of Advanced Glycation End Products and Mitohormesis in Cancer Development and Progression.Antioxidants (Basel, Switzerland) · 2025Review
- The role of oral microbiota in lung carcinogenesis through the oral-lung axis: a comprehensive review of mechanisms and therapeutic potential.Discover oncology · 2025Review
- Mimicking Gastric Cancer Collagen Reorganization with Decellularized ECM-Based Scaffolds.Biology · 2025Review
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Metabolic Effects of the Cancer Metastasis Modulator MEMO1.Metabolites · 2025Article
- Lysyl hydroxylase 2 glucosylates collagen VI to drive lung cancer progression.The Journal of clinical investigation · 2025Article
- To investigate the tumor promotion role of PLOD3 in colorectal cancer and its potential as a prognostic biomarker and therapeutic target.Scientific reports · 2025Article
- The microbiota in breast cancer: dysbiosis, microbial metabolites, and therapeutic implications.American journal of cancer research · 2025Review
- TDERS, an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer: a multicohort study.Journal of the National Cancer Center · 2024Article
- The Role of Adipocytes Recruited as Part of Tumor Microenvironment in Promoting Colorectal Cancer Metastases.International journal of molecular sciences · 2024Review
- Trends in confinement-induced cell migration and multi-omics analysis.Analytical and bioanalytical chemistry · 2024Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) was associated with elevation of cytoplasmic succinate during the EMT process. Silencing of PLOD2 expression in breast cancer cells reduced succinate levels and inhibited cancer cell mesenchymal phenotypes and stemness, which was accompanied by elevated 5hmC levels in chromatin. Importantly, exogenous succinate rescued cancer cell stemness and 5hmC levels in PLOD2-silenced cells, suggesting that PLOD2 promotes cancer progression at least partially through succinate. These results reveal the previously unidentified function of succinate in enhancing cancer cell plasticity and stemness.
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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.