Affinage

ENO2

Gamma-enolase · UniProt P09104

Length
434 aa
Mass
47.3 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ENO2 (neuron-specific enolase, NSE) is a glycolytic enzyme whose expression switches on during neuronal maturation, replacing the non-neuronal isoform as neurons morphologically and functionally differentiate (PMID:6769532, PMID:3587757). Beyond its housekeeping role in catalyzing 2-phosphoglycerate to phosphoenolpyruvate (PEP), ENO2 functions as a driver of aerobic glycolysis (the Warburg effect) that supports proliferation, migration, and stress adaptation across diverse cancers, including glioblastoma, acute lymphoblastic leukemia, head and neck and colorectal carcinomas, and in 3D anchorage-independent growth (PMID:22185371, PMID:29689546, PMID:36588153, PMID:36945054). A key non-canonical mechanism is metabolite-mediated signaling: ENO2-derived PEP selectively inhibits HDAC1, increasing β-catenin acetylation and activating β-catenin signaling to drive neuroendocrine differentiation and antiangiogenic therapy resistance (PMID:37667133). ENO2 additionally couples to AKT/GSK-3β signaling to promote glycolysis and glucocorticoid resistance, and controls PKM2 protein stability and nuclear translocation via the ubiquitin-proteasome and AKT pathways, linking it to CCND1-associated cell cycle progression (PMID:29689546, PMID:36588153). Through protein and RNA interactions ENO2 also acts independently of its catalytic function—binding lncRNA CYTOR and LATS1 to inhibit YAP1 phosphorylation and trigger EMT (PMID:35954207)—and can be exported in exosomes to reprogram macrophage polarization toward an M2 state via NF-κB and GSK3β/β-catenin/c-Myc pathways (PMID:31191019, PMID:38250157). ENO2 enzymatic activity is regulated post-translationally by SIRT1-dependent deacetylation (PMID:31202897) and inhibited by physical interaction with the c-H-ras splice product p19(ras) (PMID:19713034). Its expression is controlled transcriptionally and epigenetically—by the let-7d/KDM3A demethylation axis in trophoblasts (PMID:34350711) and, in yeast, by RAP1/ABFI/GCR1 acting through defined upstream activation sites (PMID:3537717, PMID:2201905, PMID:8455635).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1980 Medium

    Established that ENO2 is the neuronally-restricted enolase isoform whose induction tracks neuronal differentiation, defining it as a maturation marker distinct from the non-neuronal isoform.

    Evidence Radioimmunoassay of enolase isoenzymes across rat brain development with regional/temporal profiling, confirmed by in situ hybridization in human brain

    PMID:3587757 PMID:6769532

    Open questions at the time
    • Does not establish the molecular trigger of the NNE-to-NSE switch
    • Functional consequence of neuron-restricted expression not addressed
  2. 1990 High

    Dissected the cis- and trans-regulatory logic of yeast ENO2 transcription, showing overlapping RAP1/ABFI/GCR1 binding sites within upstream activation sequences mediate both glucose-dependent activation and GCR1-dependent repression.

    Evidence Deletion mapping of 5' flanking sequences, DNase I footprinting, EMSA, and in vivo expression assays in gcr1 null strains on glucose vs. gluconeogenic carbon sources

    PMID:2201904 PMID:2201905 PMID:3537717 PMID:8455635

    Open questions at the time
    • Regulatory logic established in yeast, not mapped to mammalian ENO2 promoter
    • Does not connect transcriptional control to enzyme function
  3. 2009 Medium

    Identified the first physical regulator of mammalian ENO2 activity, showing p19(ras) binds and inhibits NSE enzymatic activity to suppress tumor cell proliferation.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation (endogenous and overexpression), in vitro enzyme activity assay, and proliferation assays in H1299 cells

    PMID:19713034

    Open questions at the time
    • Structural basis of the inhibitory interaction not defined
    • Physiological contexts where p19(ras) regulates ENO2 not established
  4. 2011 Medium

    Demonstrated a functional pro-survival role for ENO2 in cancer, linking its stress-induced upregulation to migration and therapy resistance.

    Evidence siRNA knockdown in glioblastoma cells with migration, viability, and drug/radiation sensitivity readouts under hypoxia and serum starvation; nuclear/cytoplasmic localization in transformed breast epithelial cells

    PMID:22098917 PMID:22185371

    Open questions at the time
    • Mechanism linking ENO2 to resistance not resolved at this stage
    • Functional significance of nuclear ENO2 localization not established
  5. 2018 Medium

    Connected ENO2 to oncogenic signaling, showing it activates AKT/GSK-3β to drive glycolysis, proliferation, and glucocorticoid resistance.

    Evidence shRNA knockdown, proliferation and glucose consumption assays, Western blotting, and in vivo tumorigenesis in NOD/SCID mice, with 2-deoxyglucose combination

    PMID:29689546

    Open questions at the time
    • Whether ENO2 acts on AKT signaling enzymatically or non-enzymatically not distinguished
    • Direct AKT-pathway interaction partner not identified
  6. 2019 Medium

    Revealed ENO2 as both a post-translationally regulated enzyme and an intercellular signaling molecule—deacetylated by SIRT1 to control catalytic activity, and exported via exosomes to reprogram macrophages through NF-κB.

    Evidence GST pull-down/LC-MS/MS and Co-IP for SIRT1 binding with acetylation and activity assays; exosome isolation, macrophage co-culture, and p50 nuclear translocation assays in lymphoma models in vitro and in vivo

    PMID:31191019 PMID:31202897

    Open questions at the time
    • Specific acetylated lysine residues controlling activity not mapped
    • Mechanism of ENO2 packaging into exosomes unknown
  7. 2021 Medium

    Defined an epigenetic regulatory axis controlling ENO2 expression, with KDM3A demethylating the locus to activate it and let-7d suppressing KDM3A to silence it.

    Evidence Dual luciferase reporter assays, ChIP for KDM3A at the ENO2 locus, gain/loss-of-function, and an in vivo preeclampsia rat model in trophoblasts

    PMID:34350711

    Open questions at the time
    • Whether this axis operates outside trophoblasts not tested
    • Direct demethylase enzymatic action on ENO2 chromatin not biochemically isolated
  8. 2022 Medium

    Uncovered a glycolysis-independent function of ENO2 in metastasis, acting as a scaffold with lncRNA CYTOR and LATS1 to inhibit YAP1 phosphorylation and drive EMT.

    Evidence Knockdown/overexpression with migration/invasion assays, Co-IP of the ENO2-CYTOR-LATS1 complex, YAP1 phosphorylation analysis, and clinical CRC sample correlation

    PMID:35954207

    Open questions at the time
    • Structural basis of the ternary complex not resolved
    • Whether RNA binding is direct or bridged by other factors unclear
  9. 2023 High

    Established the landmark non-canonical mechanism in which ENO2's metabolic product PEP acts as an endogenous HDAC1 inhibitor to activate β-catenin and drive neuroendocrine differentiation and therapy resistance, while confirming ENO2-driven glycolytic flux sustains anchorage-independent tumor growth.

    Evidence In vitro HDAC1 activity assay with PEP, β-catenin acetylation/pathway analysis, ENO2 inhibitor treatment in drug-resistant CRC xenografts and human samples; siRNA knockdown across four lung/breast lines with lactate and spheroid readouts

    PMID:36945054 PMID:37667133

    Open questions at the time
    • Quantitative threshold of PEP needed to inhibit HDAC1 in vivo not defined
    • Whether PEP-HDAC1 inhibition operates in non-malignant neurons unknown
  10. 2024 Medium

    Refined the exosomal mechanism, showing transferred ENO2 reprograms macrophage glycolysis via the GSK3β/β-catenin/c-Myc pathway to promote M2 polarization and tumor progression.

    Evidence Exosome uptake assays, in vitro and in vivo macrophage polarization, pathway inhibition, and bioinformatics in DLBCL

    PMID:38250157

    Open questions at the time
    • Whether transferred ENO2 acts enzymatically or as a signaling protein in recipient macrophages not resolved
    • Receptor/uptake route for ENO2-bearing exosomes unknown
  11. 2025 Medium

    Extended ENO2's glycolytic-angiogenic role beyond cancer, showing FGF2-induced ENO2 supports endothelial glycolysis and pathological retinal neovascularization.

    Evidence DIA proteomics, siRNA knockdown, tube formation/migration/proliferation assays, and ENO2 inhibitor (AP-III-a4) in the oxygen-induced retinopathy mouse model

    PMID:39854009

    Open questions at the time
    • Mechanism linking FGF2 signaling to ENO2 induction not defined
    • Whether the PEP-HDAC1 axis contributes to angiogenesis not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ENO2's canonical glycolytic catalysis, its moonlighting metabolite-signaling (PEP-HDAC1), and its non-enzymatic scaffolding/exosomal roles are coordinated within a single cell—and whether these mechanisms operate in its native neuronal context—remains unresolved.
  • No structural model integrating catalytic and non-catalytic functions
  • Native neuronal function beyond being a differentiation marker uncharacterized
  • No Mendelian disease link established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016829 lyase activity 2 GO:0003723 RNA binding 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 3
Partners
CYTORHDAC1LATS1P19(RAS)PKM2SIRT1

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1980 Neuron-specific enolase (NSE/ENO2) is expressed specifically in neurons (not glial cells) of mature brain, with levels very low in embryonic brain and increasing coincident with morphological and functional neuronal maturation, consistent with a developmental switch from non-neuronal enolase (NNE/ENO1) to NSE during neuronal differentiation. Radioimmunoassay of isoenzyme content during rat brain development, with regional and temporal profiling Brain research Medium 6769532
1986 In yeast, ENO2 contains two upstream activation site (UAS) cis-acting regulatory regions immediately flanking position 461 bp upstream of the transcriptional initiation site; either UAS alone is sufficient for glucose-dependent induction and normal expression on gluconeogenic carbon sources, but deletion of both abolishes expression. Small deletions within the UAS permit normal expression on gluconeogenic sources but abolish glucose-dependent induction, identifying a specific cis-acting sequence mediating glucose induction. Deletion mapping of ENO2 5' flanking sequences fused to ENO1 coding sequences; integration at ENO1 locus; expression monitored on glucose vs. gluconeogenic carbon sources Molecular and cellular biology High 3537717
1990 Three distinct protein-binding sites exist within the upstream activation sites of yeast ENO2: RAP1 protein binds sequences overlapping UAS1; ABFI (autonomously replicating sequence-binding factor) binds sequences within the UAS2 element; and EBF1 (enolase-binding factor) binds sequences overlapping UAS2 of ENO1. The ABFI-binding site in ENO2 overlaps sequences required for UAS2 activity and for repression of ENO2 in gcr1 null mutants, indicating ABFI, like RAP1, can mediate both positive and negative regulation. DNase I footprinting, gel mobility shift assays, deletion analysis in vivo, identification of RAP1 and ABFI by protein purification and binding Molecular and cellular biology High 2201905
1990 In yeast, ABFI is identified as the major protein binding the UAS/repression site of ENO2; deletion of this site permits wild-type ENO2 expression in gcr1 null strains, demonstrating that ABFI-bound sequences are required both for transcriptional activation in wild-type and for GCR1-dependent repression; the UAS/repression site alone is sufficient for transcriptional activation but not sufficient for repression in gcr1 backgrounds. Deletion mapping in gcr1 null strains, gel mobility shift assays identifying ABFI, in vivo transcription assays with UAS-less promoter cassettes Molecular and cellular biology High 2201904
1990 Human ENO2 gene localizes to chromosome region 12p13, as determined by in situ hybridization; additional minor hybridization to 1p36 likely reflects cross-hybridization to ENO1, and a signal at chromosome 17 may represent another enolase family member. In situ hybridization of human ENO2 cDNA to chromosomes Cytogenetics and cell genetics Medium 2249478
1990 NSE immunoreactivity and NSE mRNA both increase in rat cerebellar Purkinje cells from postnatal day 3 to 9, but thereafter NSE-immunoreactive Purkinje cell somata decrease in number while mRNA remains detectable in somata through adulthood, with distinct NSE immunoreactivity remaining in Purkinje cell axons. This discrepancy suggests negative translational control and/or axoplasmic transport of NSE protein. Immunohistochemistry and in situ hybridization in rat cerebellum across postnatal development Brain research. Developmental brain research Medium 2350885
1987 NSE mRNA is expressed specifically in neurons (not glia or liver cells) in human brain, as detected by in situ hybridization with probes from the 3' untranslated region of ENO2 in autopsy brain samples from controls and Alzheimer's disease patients. In situ hybridization with biotinylated DNA and RNA probes in human autopsy brain tissue Neuroscience letters Medium 3587757
1993 A 60-bp ENO2 sequence is sufficient to confer high-level, GCR1-dependent transcriptional activation; it can be subdivided into a 30-bp region containing overlapping RAP1 and GCR1 binding sites (not sufficient alone for activation) and a 30-bp region with a novel GCR1-independent enhancer element. The overlapping ABFI/RAP1 sites upstream function together with the GCR1/RAP1-binding sequences to stage transcriptional activation. Enhancerless CYC1 promoter fusion assay, deletion mapping, in vivo transcription quantification in gcr1 null strains Molecular and cellular biology High 8455635
2009 p19(ras), an alternative splicing product of c-H-ras, physically interacts with NSE (ENO2) and inhibits its enzymatic activity; co-immunoprecipitation confirmed the interaction both endogenously and in overexpression systems; p19(ras) also inhibits enolase alpha activity in vitro. The interaction suppresses lung cancer cell proliferation that was increased by NSE. Yeast two-hybrid identification of NSE as p19(ras)-binding partner; co-immunoprecipitation in endogenous and overexpression systems; in vitro enzymatic activity assay; cell proliferation assay in H1299 cells Cancer letters Medium 19713034
2011 ENO2 (NSE) is upregulated in GBM cells under cellular stress conditions (serum starvation and hypoxia); NSE knockdown by siRNA reduces GBM cell migration and sensitizes cells to hypoxia, radiotherapy, and temozolomide, establishing a functional role for ENO2 in stress adaptation and resistance in glioblastoma cells. qPCR under different culture conditions; siRNA knockdown of NSE; Electric cell-substrate impedance sensing (ECIS) for migration; MTS viability assay after irradiation and temozolomide BMC cancer Medium 22185371
2011 ENO2 (NSE) expressed in MCF-10A breast epithelial cells transformed by arsenite (As+3) or cadmium (Cd+2) localizes to both cytoplasm and nucleus, whereas ENO1 localizes only to cytoplasm; cytoplasmic ENO2 co-localizes with ENO1. Both acute and chronic exposure to As+3 or Cd+2 significantly induces ENO2 expression with no effect on ENO1 expression. Immunofluorescence localization; Western blot; acute and chronic metal exposure of MCF-10A cells Cancer cell international Low 22098917
2018 ENO2 promotes ALL cell growth, glycolysis, and glucocorticoid resistance; mechanistically, ENO2 upregulates glycolysis-related genes and enhances AKT activity with subsequent GSK-3β phosphorylation, inducing cell proliferation and glycolysis. Silencing ENO2 with shRNAs inhibits these effects, and combined ENO2 silencing plus 2-deoxyglucose synergistically inhibits leukemia cell survival. shRNA knockdown; Cell Counting Kit-8 proliferation assay; glucose consumption assay; Western blotting; in vivo tumorigenesis in NOD/SCID mice Cellular physiology and biochemistry Medium 29689546
2019 NSE (ENO2) from DLBCL lymphoma cells is transferred to macrophages via exosomes, whereupon NSE enhances nuclear p50 translocation and suppresses classical NF-κB activity in macrophages, promoting M2 polarization and migration of macrophages, thereby promoting lymphoma progression in vitro and in vivo. Functional overexpression/knockdown studies in lymphoma cell lines; exosome isolation; macrophage co-culture; in vitro and in vivo (mouse) experiments; Western blotting for p50 nuclear translocation Cancer management and research Medium 31191019
2019 SIRT1 physically binds NSE (ENO2) and PKM in rat brain tissue; modulation of SIRT1 enzymatic activity (by agonist SRT1720 or antagonist EX527, or by SIRT1 overexpression/knockout) significantly affects the acetylation level of endogenous NSE, and changes in NSE acetylation affect its catalytic glycolytic activity. GST pull-down followed by LC-MS/MS identification; co-immunoprecipitation; SIRT1 agonist/antagonist treatment; SIRT1 overexpression and knockout; measurement of NSE catalytic activity Biochimica et biophysica acta. Proteins and proteomics Medium 31202897
2021 ENO2 promotes cell proliferation and glycolysis in HNSCC partially by controlling PKM2 protein stability and nuclear translocation: loss of ENO2 promotes PKM2 degradation via the ubiquitin-proteasome pathway and prevents nuclear translocation of PKM2 by inactivating AKT signaling, blocking PKM2-mediated glycolytic flux and CCND1-associated cell cycle progression. qRT-PCR, Western blotting, immunofluorescence, immunoprecipitation, ChIP-PCR, ATP and glucose level assays; ENO2 inhibitor AP-III-a4 in preclinical mouse model Journal of experimental & clinical cancer research Medium 36588153
2022 ENO2 promotes colorectal cancer cell migration and invasion through interaction with lncRNA CYTOR; this interaction does not depend on glycolysis regulation. CYTOR mediates ENO2 binding to LATS1, competitively inhibiting YAP1 phosphorylation and triggering epithelial-mesenchymal transition (EMT). ENO2 knockdown and overexpression; migration/invasion assays; co-immunoprecipitation of ENO2-CYTOR-LATS1 complex; YAP1 phosphorylation analysis; TCGA/GEO database analysis; 184 local CRC samples Cells Medium 35954207
2023 ENO2-derived metabolite phosphoenolpyruvate (PEP) selectively inhibits HDAC1 activity, increasing acetylation of β-catenin and activating the β-catenin pathway in colorectal cancer, driving resistance to antiangiogenic therapy. ENO2 overexpression induces neuroendocrine differentiation and promotes malignant behavior; ENO2 inhibitors (AP-III-a4 or POMHEX) synergize with antiangiogenic drugs in vitro and in drug-resistant CRC xenograft mouse models. CRC mouse models and human participant samples; in vitro HDAC1 activity assay with PEP; β-catenin acetylation and pathway analysis; ENO2 inhibitor treatment in vivo Nature metabolism High 37667133
2023 ENO2 and ALDOC are required for anchorage-independent 3D tumor spheroid growth across lung and breast cancer cell lines; siRNA-mediated knockdown of ENO2 significantly reduces lactate production, viability, and spheroid size in H460, HCC827, MCF7, and T47D cell lines, demonstrating that ENO2-driven glycolytic flux supports anchorage-independent survival. siRNA knockdown; multi-omics (transcriptomics, proteomics, metabolomics); lactate production assay; viability and spheroid size measurement in 3D culture Journal of experimental & clinical cancer research Medium 36945054
2024 DLBCL-derived exosomal ENO2 is assimilated by macrophages and modulates macrophage polarization (increased M2, decreased M1) through reprogramming glycolysis via the GSK3β/β-catenin/c-Myc signaling pathway, thereby promoting DLBCL cell proliferation, migration, and invasion in vitro and in vivo. Exosome isolation and uptake assays; in vitro and in vivo macrophage polarization experiments; pathway inhibition assays; bioinformatics analysis International journal of biological sciences Medium 38250157
2021 ENO2 expression in trophoblasts is regulated epigenetically: the histone demethylase KDM3A binds the ENO2 locus and reduces its methylation, promoting ENO2 expression; let-7d miRNA directly targets KDM3A to suppress it, resulting in increased ENO2 methylation and reduced ENO2 expression. Overexpression of let-7d suppresses trophoblast proliferation, migration, and invasion, which can be rescued by restoring ENO2 expression. Dual luciferase reporter assay for let-7d/KDM3A and let-7d/ENO2 interactions; ChIP experiment identifying KDM3A methylation of ENO2 locus; gain/loss-of-function; in vivo PE rat model Journal of cellular and molecular medicine Medium 34350711
2022 E2F1 transcription factor upregulates ENO2 expression to promote the Warburg effect (increased glucose uptake, lactate production, ATP generation) and cell viability and invasion in Ewing sarcoma; altering E2F1 expression correspondingly changes ENO2 levels and aerobic glycolysis. E2F1 overexpression/knockdown; glucose uptake, lactate production, ATP generation assays; cell viability and invasion assays Molecular medicine reports Low 35621141
2025 FGF2 stimulation of human retinal microvascular endothelial cells upregulates ENO2 protein levels and glycolytic activity; ENO2 knockdown diminishes glycolytic activity and impairs angiogenic processes (tube formation, migration, proliferation). The ENO2 inhibitor AP-III-a4 alleviates retinal neovascularization in the oxygen-induced retinopathy mouse model in vivo. Data-independent acquisition proteomics; qRT-PCR and Western blot; siRNA knockdown; transwell/EdU/tube formation assays; ENO2 inhibitor treatment in OIR mouse model; immunofluorescence Investigative ophthalmology & visual science Medium 39854009

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1980 Developmental profile of neuron-specific (NSE) and non-neuronal (NNE) enolase. Brain research 204 6769532
2019 The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients. Journal of translational medicine 149 30849967
2003 Protein S-100B, neuron-specific enolase (NSE), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) and blood of neurological patients. Brain research bulletin 106 12909296
2017 Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer. Life sciences 97 29247745
1990 Multiple factors bind the upstream activation sites of the yeast enolase genes ENO1 and ENO2: ABFI protein, like repressor activator protein RAP1, binds cis-acting sequences which modulate repression or activation of transcription. Molecular and cellular biology 95 2201905
2007 Generation of a transgenic zebrafish model of Tauopathy using a novel promoter element derived from the zebrafish eno2 gene. Nucleic acids research 92 17897967
2021 S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy. Neurosurgical review 89 34709508
2008 Nucleosomes, ProGRP, NSE, CYFRA 21-1, and CEA in monitoring first-line chemotherapy of small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 86 19047109
2009 NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children. Neurology 70 19221293
1986 Identification of a regulatory region that mediates glucose-dependent induction of the Saccharomyces cerevisiae enolase gene ENO2. Molecular and cellular biology 69 3537717
2018 ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 67 29689546
2005 S100B and NSE serum levels in patients with Parkinson's disease. Parkinsonism & related disorders 63 15619461
2014 Combining NSE and S100B with clinical examination findings to predict survival after resuscitation from cardiac arrest. Resuscitation 60 24795283
2024 Tumor-derived Exosomal ENO2 Modulates Polarization of Tumor-associated Macrophages through Reprogramming Glycolysis to Promote Progression of Diffuse Large B-cell Lymphoma. International journal of biological sciences 58 38250157
1998 Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma. Cancer 52 9506348
2011 Neuronal markers are expressed in human gliomas and NSE knockdown sensitizes glioblastoma cells to radiotherapy and temozolomide. BMC cancer 51 22185371
2009 Serum concentrations of s100b and NSE in migraine. Headache 50 18783450
2015 ENO2 activity is required for the development and reproductive success of plants, and is feedback-repressed by AtMBP-1. The Plant journal : for cell and molecular biology 48 25620024
2001 Expression of S100a, vimentin, NSE, and melan A/MART-1 in seven canine melanoma cells lines and twenty-nine retrospective cases of canine melanoma. Veterinary pathology 48 11467477
2008 ProGRP and NSE in therapy monitoring in patients with small cell lung cancer. Anticancer research 46 19031951
2023 Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development. Journal of experimental & clinical cancer research : CR 45 36588153
2022 Electrochemical neuron-specific enolase (NSE) immunosensor based on CoFe2O4@Ag nanocomposite and AuNPs@MoS2/rGO. Analytica chimica acta 44 35256133
2018 Diagnostic value of NT-proCNP compared to NSE and S100B in cerebrospinal fluid and plasma of patients with sepsis-associated encephalopathy. Neuroscience letters 44 30423400
2023 ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis. Journal of experimental & clinical cancer research : CR 42 36945054
2018 Serial measurement of S100B and NSE in pediatric traumatic brain injury. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 38 30171330
2022 ENO2 Promotes Colorectal Cancer Metastasis by Interacting with the LncRNA CYTOR and Activating YAP1-Induced EMT. Cells 37 35954207
2023 ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy. Nature metabolism 35 37667133
2013 S100B and NSE as useful postmortem biochemical markers of traumatic brain injury in autopsy cases. Journal of neurotrauma 34 23796187
1995 Discriminant analysis on small cell lung cancer and non-small cell lung cancer by means of NSE and CYFRA-21.1. The European respiratory journal 34 7589398
2020 The Combination of CA125 and NSE Is Useful for Predicting Liver Metastasis of Lung Cancer. Disease markers 33 33376560
2018 Serum ProGRP and NSE levels predicting small cell lung cancer transformation in a patient with ALK rearrangement-positive non-small cell lung cancer: A case report. Oncology letters 33 30214557
2013 CEA, SCC and NSE levels in exhaled breath condensate--possible markers for early detection of lung cancer. Journal of breath research 33 24185583
2012 Effects of hypothermia on NSE and S-100 protein levels in CSF in neonates following hypoxic/ischaemic brain damage. Acta paediatrica (Oslo, Norway : 1992) 32 22452413
2006 S100B and NSE serum levels in obstructive sleep apnea syndrome. Sleep medicine 32 16750933
1993 A complex regulatory element from the yeast gene ENO2 modulates GCR1-dependent transcriptional activation. Molecular and cellular biology 32 8455635
1987 Localization of neuron-specific enolase (NSE) mRNA in human brain. Neuroscience letters 32 3587757
2011 Arsenic, cadmium and neuron specific enolase (ENO2, γ-enolase) expression in breast cancer. Cancer cell international 31 22098917
1990 Ontogenic changes in expression of neuron-specific enolase (NSE) and its mRNA in the Purkinje cells of the rat cerebellum: immunohistochemical and in situ hybridization study. Brain research. Developmental brain research 31 2350885
2023 Association of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP with Clinicopathological Characteristics and Chemotherapeutic Outcomes of Lung Cancer. Laboratory medicine 30 36282321
2020 Increased Cerebrospinal Fluid S100B and NSE Reflect Neuronal and Glial Damage in Parkinson's Disease. Frontiers in aging neuroscience 30 32792937
1990 Localisation of neurone-specific enolase (ENO2) to 12p13. Cytogenetics and cell genetics 28 2249478
2020 IncRNA ZFAS1 contributes to the radioresistance of nasopharyngeal carcinoma cells by sponging hsa-miR-7-5p to upregulate ENO2. Cell cycle (Georgetown, Tex.) 27 33342344
2014 Hypermethylation of the enolase gene (ENO2) in autism. European journal of pediatrics 27 24737292
2015 Immunohistochemical investigation of S100 and NSE in cases of traumatic brain injury and its application for survival time determination. Journal of neurotrauma 26 25211554
1994 Serum neuron-specific enolase (S-NSE) in progressive small-cell lung cancer (SCLC). British journal of cancer 26 7917935
2017 Serum Levels of S100b and NSE Proteins in Patients with Non-Transfusion-Dependent Thalassemia as Biomarkers of Brain Ischemia and Cerebral Vasculopathy. International journal of molecular sciences 25 29244749
2008 Serum concentration of NSE and S-100b during LVAD in non-resuscitated patients. Resuscitation 25 18617311
2020 Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events. In vivo (Athens, Greece) 24 32871787
2020 Diagnostic Value and Clinical Significance of Combined Detection of Serum Markers CYFRA21-1, SCC Ag, NSE, CEA and ProGRP in Non-Small Cell Lung Carcinoma. Clinical laboratory 23 33180443
2016 The diagnostic value of serum CEA, NSE and MMP-9 for on-small cell lung cancer. Open medicine (Warsaw, Poland) 23 28352768
2011 Effect of endurance exercise training on the expression of GFAP, S100B, and NSE in the striatum of chronic/progressive mouse model of Parkinson's disease. NeuroRehabilitation 23 21725169
1990 Sequences within an upstream activation site in the yeast enolase gene ENO2 modulate repression of ENO2 expression in strains carrying a null mutation in the positive regulatory gene GCR1. Molecular and cellular biology 22 2201904
2019 NSE from diffuse large B-cell lymphoma cells regulates macrophage polarization. Cancer management and research 21 31191019
2006 Plasma S100beta and NSE levels and progression in multiple sclerosis. Journal of the neurological sciences 21 17187827
2008 Effects of neuregulin on expression of MMP-9 and NSE in brain of ischemia/reperfusion rat. Journal of molecular neuroscience : MN 20 18830828
2022 ENO2 affects the EMT process of renal cell carcinoma and participates in the regulation of the immune microenvironment. Oncology reports 18 36562383
2020 Glial and neuronal markers in bipolar disorder: A meta-analysis testing S100B and NSE peripheral blood levels. Progress in neuro-psychopharmacology & biological psychiatry 17 32171903
2002 Enhanced expression of neuron-specific enolase (NSE) in pyothorax-associated lymphoma (PAL). Japanese journal of cancer research : Gann 17 11985791
2022 Serum S100B and NSE Levels Correlate With Infarct Size and Bladder-Bowel Involvement Among Acute Ischemic Stroke Patients. Journal of neurosciences in rural practice 16 35694066
2020 The effect of obstructive sleep apnea syndrome on serum S100B and NSE levels: a systematic review and meta-analysis of observational studies. BMC pulmonary medicine 16 32024492
2014 The role of neuron-specific enolase (NSE) and thymidine kinase (TK) levels in prediction of efficacy ofEGFR-TKIs in patients with advanced-stage NSCLC [corrected]. Anticancer research 16 25202114
1997 S-100 and NSE as serum markers in melanoma. Acta oncologica (Stockholm, Sweden) 16 9490097
1986 Immunohistochemical study of S-100 protein and neuron specific enolase (NSE) in melanocytes and the related tumors. Acta histochemica 16 3101377
1985 Differentiation markers (S-100, GFAP, NSE and D2) in fetal rat brain cells during malignant transformation in cell culture. Journal of neuro-oncology 16 4031972
2024 ENO2, a Glycolytic Enzyme, Contributes to Prostate Cancer Metastasis: A Systematic Review of Literature. Cancers 15 39061144
2007 Brain injury markers (S100B and NSE) in chronic cocaine dependents. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) 15 17650535
2021 Impact of HSP90α, CEA, NSE, SCC, and CYFRA21-1 on Lung Cancer Patients. Journal of healthcare engineering 14 34721827
2021 NSE, positively regulated by LINC00657-miR-93-5p axis, promotes small cell lung cancer (SCLC) invasion and epithelial-mesenchymal transition (EMT) process. International journal of medical sciences 14 34790052
2016 The neonatal levels of TSB, NSE and CK-BB in autism spectrum disorder from Southern China. Translational neuroscience 14 28123815
2006 Fenretinide-induced neuronal differentiation of ARPE-19 human retinal pigment epithelial cells is associated with the differential expression of Hsp70, 14-3-3, pax-6, tubulin beta-III, NSE, and bag-1 proteins. Molecular vision 14 17110918
2003 Pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in therapy control of patients with small-cell lung cancer. Clinical laboratory 14 12593474
2022 Reduced Concentrations of NSE, S100β, Aβ, and Proinflammatory Cytokines in Elderly Patients Receiving Ultrasound-Guided Combined Lumbar Plexus-Sciatic Nerve Block during Hip Replacement. Genetics research 13 35356751
2009 Comparison of S100B and NSE between cardiac surgery and interventional therapy for children. Pediatric cardiology 13 19471994
2009 p19(ras) Represses proliferation of non-small cell lung cancer possibly through interaction with Neuron-Specific Enolase (NSE). Cancer letters 13 19713034
2024 Performance of biomarkers NF-L, NSE, Tau and GFAP in blood and cerebrospinal fluid in rat for the detection of nervous system injury. Frontiers in neuroscience 12 38292901
2022 E2F1 promotes Warburg effect and cancer progression via upregulating ENO2 expression in Ewing sarcoma. Molecular medicine reports 12 35621141
2020 Expression patterns and clinical significances of ENO2 in lung cancer: an analysis based on Oncomine database. Annals of translational medicine 12 32566576
2020 Correlation of changes in serum S100β, NSE and inflammatory factor levels with MMSE and MoCA in intracranial tumor patients with cognitive impairment. Oncology letters 12 32724442
2011 Experimental subacute spinal cord compression: correlation of serial S100B and NSE serum measurements, histopathological changes, and outcome. Neurological research 12 21535942
2022 Application Value of Serum TK1 and PCDGF, CYFRA21-1, NSE, and CEA plus Enhanced CT Scan in the Diagnosis of Nonsmall Cell Lung Cancer and Chemotherapy Monitoring. Journal of oncology 11 35368891
2020 Sodium valproate combined with levetiracetam in pediatric epilepsy and its influence on NSE, IL-6, hs-CRP and electroencephalogram improvement. Experimental and therapeutic medicine 11 32782515
2019 SIRT 1 binding with PKM and NSE and modulate their acetylation and activities. Biochimica et biophysica acta. Proteins and proteomics 11 31202897
2013 NSE can predict the sensitivity to definitive chemoradiotherapy of small cell carcinoma of esophagus. Medical oncology (Northwood, London, England) 11 24307347
1988 S-100 protein and neuron specific enolase (NSE) expression by chordomas in relation to the composition of their stromal mucosubstances. Pathology, research and practice 11 3420027
2021 Overexpression of let-7d explains down-regulated KDM3A and ENO2 in the pathogenesis of preeclampsia. Journal of cellular and molecular medicine 9 34350711
2015 Elevated Serum Levels of NSE and S-100β Correlate with Increased Risk of Acute Cerebral Infarction in Asian Populations. Medical science monitor : international medical journal of experimental and clinical research 9 26124190
2011 Serum concentrations of NSE and S100B in spinocerebellar ataxia type 3/Machado-Joseph disease. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 9 21743141
2024 NSE and S100β as serum alarmins in predicting neurological outcomes after cardiac arrest. Scientific reports 8 39462073
2023 Correlation between HRCT signs and levels of CA125, SCCA, and NSE for different pathological types of lung cancer. European review for medical and pharmacological sciences 8 37203842
2023 ENO2 as a Biomarker Regulating Energy Metabolism to Promote Tumor Progression in Clear Cell Renal Cell Carcinoma. Biomedicines 8 37760940
2023 Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy. International journal of molecular sciences 8 38203674
2022 Based on multiple machine learning to identify the ENO2 as diagnosis biomarkers of glaucoma. BMC ophthalmology 8 35366826
2022 GFAP and Neuron Specific Enolase (NSE) in the Serum of Suicide Attempters. Medical journal of the Islamic Republic of Iran 8 36447551
2020 Serum NO, S100B, NSE concentrations in migraine and their relationship. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 8 33317735
2017 Clinical significance of dynamic measurements of seric TNF-α, HMGBl, and NSE levels and aEEG monitoring in neonatal asphyxia. European review for medical and pharmacological sciences 8 29077174
1993 Soluble interleukin-2 receptors (sIL-2R) and neuron specific enolase (NSE) in small cell lung carcinoma. Anticancer research 8 8386493
2025 ENO2-Regulated Glycolysis in Endothelial Cells Contributes to FGF2-Induced Retinal Neovascularization. Investigative ophthalmology & visual science 7 39854009
2024 Effects of parecoxib on postoperative cognitive dysfunction and serum levels of NSE and S100β in elderly patients undergoing surgery. European review for medical and pharmacological sciences 7 38235879
2023 Relationships of serum VILIP-1, NSE, and ADP levels with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia: a retrospective, observational study. The Journal of international medical research 7 37194201
2010 [Diagnostic value of ProGRP and NSE for small cell lung cancer: a meta-analysis]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 7 21159242

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