ArticleNature metabolism2023
ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 38 citations in OpenAlex.
- [Research progress of metabolomics in the pathogenesis and treatment of constipation in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- Amino-acids-mTORC1-driven DDA1 phosphorylation promotes DNA repair and glioblastoma progression.Cell communication and signaling : CCS · 2026Article
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- PKM2 Lactylation Promotes Colorectal Cancer Vasculogenic Mimicry and Bevacizumab Resistance by Facilitating FOSL1 Super-enhancer Formation.Cancer research · 2026Article
- Enolase 2-mediated lactylation-dependent disruption of the GNL3-MDM2-p53 axis in age-related osteoarthritis.Cellular & molecular biology letters · 2026Article
- HIF-1α Promotes Macrophage Extracellular Trap Formation and Exacerbates Acute Lung Injury in Neonatal Sepsis.Biomedicines · 2026Article
- Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.Nature communications · 2026Article
- ENO2 drives tumor cell-induced M2 macrophage polarization to promote colorectal cancer liver metastasis.Signal transduction and targeted therapy · 2026Article
- Extracellular CD44 lactylation impairs CD8Nature metabolism · 2026Article
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β.Cell death discovery · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Proteomics of malignant pleural mesothelioma under hypoxic and normoxic conditions in a large animal (porcine) tumor model.BMC cancer · 2025Article
- Homeostasis of glucose and lipid metabolism during physiological responses to a simulated hypoxic high altitude environment.Nature communications · 2025Article
- Transcriptomic analysis identifies key genes associated with nutrient deprivation responses in infectious bursal disease virus infection.BMC genomics · 2025Article
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Molecular signatures of disulfidptosis: interplay with programmed cell death pathways and therapeutic implications in oncology.Cellular & molecular biology letters · 2025Review
- Integrative Single-Cell and Bulk RNA Sequencing Identifies a Glycolysis-Related Prognostic Signature for Predicting Prognosis in Pancreatic Cancer.International journal of molecular sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 4 institutions in 1 country.
Funding
Abstract
Metabolic reprogramming is associated with resistance to antiangiogenic therapy in cancer. However, its molecular mechanisms have not been clearly elucidated. Here, we identify the glycolytic enzyme enolase 2 (ENO2) as a driver of resistance to antiangiogenic therapy in colorectal cancer (CRC) mouse models and human participants. ENO2 overexpression induces neuroendocrine differentiation, promotes malignant behaviour in CRC and desensitizes CRC to antiangiogenic drugs. Mechanistically, the ENO2-derived metabolite phosphoenolpyruvate (PEP) selectively inhibits histone deacetylase 1 (HDAC1) activity, which increases the acetylation of β-catenin and activates the β-catenin pathway in CRC. Inhibition of ENO2 with enolase inhibitors AP-III-a4 or POMHEX synergizes the efficacy of antiangiogenic drugs in vitro and in mice bearing drug-resistant CRC xenograft tumours. Together, our findings reveal that ENO2 constitutes a useful predictive biomarker and therapeutic target for resistance to antiangiogenic therapy in CRC, and uncover a previously undefined and metabolism-independent role of PEP in regulating resistance to antiangiogenic therapy by functioning as an endogenous HDAC1 inhibitor.
Indexed as
Identifiers
What OpenQuestion holds
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.