Affinage

NDRG2

Protein NDRG2 · UniProt Q9UN36

Length
371 aa
Mass
40.8 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NDRG2 is a cytosolic adaptor/scaffold protein that suppresses proliferative and inflammatory signaling by recruiting protein phosphatases to specific substrates and by controlling protein stability through dedicated E3 ligases (PMID:24569712, PMID:36179025, PMID:33099085). Its best-defined activity is recruiting PP2A to PTEN, driving dephosphorylation of the PTEN C-terminal Ser380/Thr382/Thr383 cluster to activate PTEN and restrain PI3K-AKT signaling; loss of NDRG2 hyperphosphorylates PTEN and constitutively activates AKT (PMID:24569712). The same scaffolding logic extends to PP2A recruitment to NIK to dampen non-canonical NF-κB (PMID:26269411), and to PPM1A engagement, where cytoplasmic NDRG2 restricts Smad2/3 dephosphorylation to sustain MMP-9 transcription (PMID:36179025). NDRG2 also stabilizes adherens junctions by enhancing FBXO11-mediated ubiquitination and degradation of the E-cadherin repressor Snail (PMID:33099085). Across colorectal cancer models NDRG2 converges on the β-catenin/c-Myc axis, suppressing β-catenin nuclear translocation and TCF/LEF activity to repress Skp2, c-Myc, and downstream glycolytic and glutaminolytic programs, thereby imposing G1/S arrest and a differentiated phenotype (PMID:29343851, PMID:26317652, PMID:33162818). In the brain, NDRG2 is an astrocyte-enriched protein that interacts with the Na+/K+-ATPase β1 subunit to promote EAAT-mediated glutamate uptake, limiting excitotoxicity and behavioral hyperactivity (PMID:31250377, PMID:29058689). NDRG2 is itself a phosphorylation hub: AKT phosphorylates it at Thr-348 and PKCθ at Ser-332 downstream of insulin (PMID:14985363), while DAPK1 phosphorylates Ser-350 to promote caspase-dependent neuronal death (PMID:28141794). Its expression is repressed by c-Myc via Miz-1 and activated by KLF4 and FXR (PMID:17050536, PMID:28656310, PMID:23056173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2004 High

    Established that NDRG2 is a direct kinase substrate integrating insulin signaling, defining the regulatory phosphorylation sites that gate its activity.

    Evidence In vitro kinase assays with site-directed mutagenesis and [32P] labeling in C2C12 cells identifying Akt-Thr348 and PKCθ-Ser332

    PMID:14985363

    Open questions at the time
    • Functional consequence of each phosphosite on NDRG2 scaffold activity not resolved
    • Did not address downstream effectors of phosphorylated NDRG2
  2. 2006 High

    Showed how NDRG2 expression itself is controlled, identifying c-Myc/Miz-1 as a transcriptional repressor circuit.

    Evidence Reporter assays, ChIP, and EMSA with ectopic c-Myc and Miz-1 manipulation

    PMID:17050536

    Open questions at the time
    • Reciprocal regulation (NDRG2 repressing c-Myc) not yet connected
    • HDAC identity at the promoter unspecified
  3. 2014 High

    Defined the core molecular mechanism of NDRG2 as a phosphatase-recruiting scaffold, explaining its tumor-suppressive link to PI3K-AKT.

    Evidence Reciprocal Co-IP, phosphorylation analysis of the PTEN C-terminal cluster, and Ndrg2-knockout mice

    PMID:24569712

    Open questions at the time
    • Structural basis of the NDRG2-PTEN-PP2A ternary complex unknown
    • Which PP2A holoenzyme is recruited not specified
  4. 2015 Medium

    Generalized the scaffold model by showing NDRG2 also recruits PP2A to NIK to suppress non-canonical NF-κB.

    Evidence Forced NDRG2 expression in ATL cells with immunoprecipitation and phosphorylation assays

    PMID:26269411

    Open questions at the time
    • Single study without independent replication
    • Direct NDRG2-NIK binding versus PP2A bridging not distinguished
  5. 2016 High

    Revealed a death-promoting arm of NDRG2 regulation, showing DAPK1 phosphorylation converts NDRG2 into a pro-apoptotic neuronal factor.

    Evidence Phospho-peptide library screen, in vitro kinase assay with mutagenesis, and validation in primary neurons and Tg2576 mice

    PMID:28141794

    Open questions at the time
    • Downstream effectors linking Ser350-phospho-NDRG2 to caspase activation unknown
    • Relationship to the PTEN/AKT scaffold role unresolved
  6. 2019 High

    Identified the molecular partner underlying NDRG2's astrocytic glutamate-handling role, linking it to Na+/K+-ATPase function.

    Evidence Co-IP, glutamate uptake assays, blocking peptide, and Ndrg2-knockout mice with in vivo ischemia

    PMID:31250377

    Open questions at the time
    • Direct binding interface with β1 subunit not mapped
    • How NDRG2 mechanistically enhances pump function unclear
  7. 2018 High

    Connected NDRG2 to the β-catenin/Skp2 axis, explaining its control of CDK inhibitor stability and differentiation.

    Evidence Ndrg2 knockout mice, ChIP promoter occupancy, and NDRG2 deletion-mutant domain mapping

    PMID:29343851

    Open questions at the time
    • Mechanism by which the N-terminal domain represses β-catenin nuclear translocation unresolved
    • Direct GSK-3β regulation inferred, not demonstrated
  8. 2022 High

    Extended the phosphatase-scaffold paradigm to PPM1A/Smad signaling and demonstrated therapeutic disruptability of the interaction.

    Evidence Reciprocal Co-IP, astrocyte-specific Ndrg2 knockout, and a blocking peptide (TAT-QFNP12) in an SAH model

    PMID:36179025

    Open questions at the time
    • Whether NDRG2 inhibits PPM1A catalytic activity or sequesters substrate not distinguished
    • Generality beyond astrocytes/SAH untested
  9. 2020 High

    Established NDRG2 as a control point for adherens-junction integrity through ligase-directed Snail turnover.

    Evidence Intestine-specific Ndrg2 knockout, Co-IP of the NDRG2-FBXO11-Snail complex, ubiquitination assay, and colitis models

    PMID:33099085

    Open questions at the time
    • How NDRG2 enhances FBXO11-Snail engagement biochemically unknown
    • Direct NDRG2-FBXO11 binding interface not mapped
  10. 2017 High

    Demonstrated the physiological and behavioral consequence of NDRG2-dependent glutamate clearance in vivo.

    Evidence Ndrg2-knockout mice with microdialysis, electrophysiology, and NDRG2 peptide rescue of ADHD-like behavior

    PMID:29058689

    Open questions at the time
    • Molecular mediator of peptide rescue not defined
    • Link to specific glutamate transporter at this stage indirect

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NDRG2's distinct activities — phosphatase recruitment, E3-ligase facilitation, and ion-transporter binding — are selected in a given cell type, and whether a unifying biochemical activity underlies them, remains unresolved.
  • No structural model of any NDRG2 complex
  • No defined catalytic activity for NDRG2 itself
  • Determinants of substrate/partner selection across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 3 R-HSA-112316 Neuronal System 2 R-HSA-392499 Metabolism of proteins 2
Partners
ATP1B1FBXO11MSP58NIKPP2APPM1APRA1PTEN

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 NDRG2 is a PTEN-binding protein that recruits protein phosphatase 2A (PP2A) to PTEN, thereby promoting dephosphorylation of PTEN at the Ser380/Thr382/Thr383 cluster within the C-terminal tail; loss of NDRG2 leads to enhanced PTEN phosphorylation at this cluster, inactivating PTEN and constitutively activating the PI3K-AKT pathway. Co-immunoprecipitation, binding assays, phosphorylation analysis, cell-based overexpression/knockdown, Ndrg2-knockout mouse model Nature communications High 24569712
2015 NDRG2 also recruits PP2A to NF-κB-inducing kinase (NIK), promoting NIK dephosphorylation and thereby suppressing the non-canonical NF-κB pathway, in addition to its role in suppressing PI3K/AKT signaling via PTEN dephosphorylation. Forced expression of NDRG2 in ATL cells, immunoprecipitation, phosphorylation assays Scientific reports Medium 26269411
2004 Akt directly phosphorylates NDRG2 at Thr-348 in response to insulin, while PKCθ phosphorylates NDRG2 at Ser-332; PKCθ overexpression reduces insulin-stimulated Thr-348 phosphorylation without reducing Akt activation, suggesting cross-talk at the substrate level. In vitro kinase assay, site-directed mutagenesis, [32P]-orthophosphate labeling, phospho-Akt-substrate antibody, co-overexpression in C2C12 cells The Journal of biological chemistry High 14985363
2016 DAPK1 directly interacts with NDRG2 and phosphorylates it at Ser350 in vitro and in vivo; DAPK1-mediated phosphorylation of NDRG2-Ser350 promotes caspase-dependent neuronal cell death, and DAPK1 inhibition abolishes NDRG2-Ser350 phosphorylation and reduces neuronal death in primary neurons and mouse brain. Phospho-peptide library screening, in vitro kinase assay, Co-IP, cell-based overexpression and shRNA knockdown, primary neuron experiments, Tg2576 mouse model Cell death and differentiation High 28141794
2006 c-Myc represses NDRG2 transcription through interaction with the NDRG2 core promoter via Miz-1 and recruitment of histone deacetylases; Miz-1 association is required for c-Myc-mediated NDRG2 repression. Reporter assay, chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), ectopic c-Myc expression, Miz-1 co-expression/knockdown The Journal of biological chemistry High 17050536
2022 Cytoplasmic NDRG2 in astrocytes binds to the protein phosphatase PPM1A and restricts dephosphorylation of Smad2/3; after subarachnoid hemorrhage, this NDRG2-PPM1A interaction reduces Smad2/3 dephosphorylation, sustaining MMP-9 transcription and blood-brain barrier disruption. A blocking peptide (TAT-QFNP12) that disrupts the NDRG2-PPM1A interaction attenuates MMP-9 production and BBB damage. Co-immunoprecipitation, Ndrg2 astrocyte-specific knockout mice, phosphorylation analysis of Smad2/3, peptide competition, in vivo SAH model Science advances High 36179025
2007 NDRG2 stimulates amiloride-sensitive ENaC currents by increasing ENaC surface expression in Xenopus oocytes and Fisher rat thyroid cells; siRNA knockdown of NDRG2 reduces ENaC-mediated short-circuit current, and the stimulatory effect is at least partially additive to Sgk1. Xenopus oocyte electrophysiology, chemiluminescence surface expression assay, siRNA knockdown in Fisher rat thyroid cells, short-circuit current measurement The Journal of biological chemistry High 17652085
2006 NDRG2 physically interacts with MSP58 (58-kDa microspherule protein) via the forkhead-associated domain of MSP58; the two proteins co-localize in the nucleus during cell stress, and modulation of NDRG2 levels influences cell cycle progression together with MSP58. Yeast two-hybrid screening, GST pull-down, co-immunoprecipitation, confocal co-localization Biochemical and biophysical research communications Medium 17109818
2012 NDRG2 interacts with prenylated Rab acceptor-1 (PRA1) as identified by yeast two-hybrid screening; the interaction was confirmed by GST pull-down and immunoprecipitation. NDRG2 and PRA1 co-localize in HCT116 cells and synergistically downregulate TCF promoter activity and GSK3β phosphorylation. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, confocal microscopy, TCF/LEF luciferase reporter assay FEBS letters Medium 23068607
2009 NDRG2 expression in colon carcinoma cells reduces c-Jun phosphorylation at Ser63, attenuating AP-1 transcriptional activity and downstream cyclin D1 expression, resulting in G1/S cell cycle arrest; NDRG2 mutants lacking C-terminal phosphorylation sites lose this activity. Stable cell lines with wild-type and deletion/point mutant NDRG2, Western blotting, luciferase reporter assay, flow cytometry, siRNA rescue International journal of cancer Medium 18844221
2009 NDRG2 expression reduces TCF/LEF transcriptional activity in colon cancer cells and modulates β-catenin stability through regulation of GSK-3β activity; NDRG2 mutants lacking C-terminal phosphorylation sites lose this regulatory activity. TOPflash TCF/LEF luciferase reporter assay, Western blotting for β-catenin and GSK-3β, site-directed mutagenesis, stable cell transfection Carcinogenesis Medium 19237607
2018 NDRG2 induction of colorectal cancer cell differentiation is dependent on repression of E3 ligase Skp2, which stabilizes the CDK inhibitors p21 and p27; NDRG2 suppresses Skp2 by reducing β-catenin nuclear translocation and decreasing β-catenin/TCF occupancy on the Skp2 promoter, potentially through dephosphorylation of GSK-3β. The NH2-terminal domain of NDRG2 is required for Skp2 suppression. Ndrg2 knockout mice, shRNA knockdown, Western blotting, ChIP, promoter occupancy assay, NDRG2 deletion mutants, alkaline phosphatase (AKP) activity assay Oncogene High 29343851
2015 NDRG2 inhibits glycolysis and glutaminolysis in colorectal cancer cells by repressing c-Myc expression via suppression of β-catenin nuclear translocation, which reduces transcriptional activation of the C-MYC gene; this consequently decreases expression of GLUT1, HK2, PKM2, LDHA, ASCT2, and GLS1. Metabolite measurement (glucose/lactate/glutamine/glutamate), Western blotting, β-catenin knockdown, c-Myc knockdown, NDRG2 overexpression in colorectal cancer cells Oncotarget Medium 26317652
2020 NDRG2 ablation induces glutamine dependence via Akt-dependent inhibition of Fbw7-mediated c-Myc degradation, which increases c-Myc-driven ASCT2 (glutamine transporter) transcription; NDRG2 promotes Fbw7-dependent c-Myc degradation by inhibiting Akt, and ASCT2 restoration reverses NDRG2's inhibitory effect on EMT and metastasis. Immunoprecipitation, protein half-life assay, luciferase reporter, ChIP, mRNA-seq, NDRG2-knockout MEF cells, functional invasion/migration assays International journal of biological sciences Medium 33162818
2019 NDRG2 promotes astroglial glutamate uptake by interacting with and promoting the function of Na+/K+-ATPase β1 subunit; NDRG2 knockout reduces EAAT-mediated glutamate uptake and increases interstitial glutamate in mouse brain, leading to greater neuronal death upon glutamate challenge. Ndrg2-knockout mice, Co-IP demonstrating NDRG2-Na+/K+-ATPase β1 interaction, glutamate uptake assay in astrocytes, Na+/K+-ATPase β1 blocking peptide, neuronal death assay, in vivo ischemia model Translational stroke research High 31250377
2017 KLF4 transcriptionally activates NDRG2 by directly binding to the NDRG2 promoter; KLF4-dependent inhibition of colorectal cancer cell proliferation is dependent on NDRG2 expression, as NDRG2 knockdown abrogates the anti-proliferative effect of KLF4. Chromatin immunoprecipitation, luciferase reporter assay, MTT assay, EdU staining, colony formation, xenograft mouse model, siRNA knockdown Oncology reports Medium 28656310
2014 Farnesoid X receptor (FXR) directly controls NDRG2 transcription through IR1-type response elements identified in the first introns of the human, mouse and rat NDRG2 genes, as supported by gene reporter assays and chromatin immunoprecipitation. Gene reporter assay, chromatin immunoprecipitation, FXR ectopic expression, FXR knockout mice, non-steroidal FXR agonist treatment PloS one Medium 23056173
2008 NDRG2 overexpression in liver cancer cells specifically induces active BMP-4 expression; neutralization of BMP-4 in NDRG2-expressing cells restores MMP-9 mRNA expression and migration capacity, demonstrating that NDRG2 suppresses MMP-9 activity and migration through BMP-4 induction. NDRG2 stable overexpression, BMP-4 neutralizing antibody, recombinant BMP-4 treatment, gelatin zymography for MMP-9 activity, migration and invasion assays Biochemical and biophysical research communications Medium 19450561
2007 NDRG2 expression in breast cancer cells increases SOCS1 mRNA and protein expression in a p38 MAPK-dependent manner; this SOCS1 induction inhibits JAK2/STAT3 activation, as p38 MAPK inhibition blocks SOCS1 induction by NDRG2 and rescues STAT3 phosphorylation. Western blotting for phospho-Akt, p38, JNK, JAK2, STAT3, RT-PCR for SOCS1, p38 inhibitor treatment, stable NDRG2 overexpression Biochemical and biophysical research communications Medium 17888401
2011 NDRG2 suppresses TGF-β1/Smad3 signaling in hepatic stellate cells by reducing Smad3 transcription and phosphorylation, and increases the MMP2/TIMP2 ratio; adenovirus-mediated NDRG2 overexpression in fibrotic rat livers reduces ECM deposition and improves liver function. NDRG2 overexpression and knockdown in HSCs, Western blotting for phospho-Smad3, gelatin zymography, adenovirus delivery in dimethylnitrosamine-induced rat fibrosis model PloS one Medium 22110735
2020 NDRG2 directly interacts with NF-κB and inhibits nuclear import and DNA binding activity of the NF-κB p65 subunit in astrocytes after OxyHb treatment, reducing glutamate transporter 1 (GLT1) transcription and impairing glutamate uptake in the context of intracerebral hemorrhage. Ndrg2-knockout mice, Co-IP demonstrating NDRG2-NF-κB interaction, NF-κB nuclear translocation assay, GLT1 promoter analysis, primary astrocyte culture, ICH mouse model Brain research Medium 31843625
2020 In NDRG2-deficient astrocytes, NDRG2 loss increases NF-κB phosphorylation, activating complement C3 transcription; NDRG2 overexpression inhibits complement C3 via NF-κB suppression, reducing synaptic injury in diabetic mice. C3aR blockade rescued dendritic spine loss consistent with NDRG2/NF-κB/C3/C3aR as a signaling axis. Ndrg2 knockout and overexpression in vivo, Western blotting, immunofluorescence, electrophysiology, Golgi staining, RNA-seq and proteome sequencing with WGCNA EBioMedicine Medium 37329577
2020 NDRG2 enhances FBXO11-mediated ubiquitination and degradation of Snail (a repressor of E-cadherin), thereby maintaining E-cadherin expression and adherens junction integrity in intestinal epithelial cells; intestine-specific Ndrg2 deletion leads to Snail accumulation, E-cadherin loss, and increased intestinal permeability. Intestine-specific Ndrg2 knockout mice, Co-IP for NDRG2-FBXO11-Snail complex, ubiquitination assay, Western blotting, barrier permeability assay, DSS/TNBS colitis models EBioMedicine High 33099085
2012 NDRG2 overexpression in rat liver cells induces cell cycle arrest and apoptosis associated with induction of p53 and p21, increased Bax/Bcl-2 ratio, and inhibition of cyclin E-Cdk2; conversely, p53 upregulates NDRG2 expression in A-498 cells, suggesting a positive feedback loop. Adenoviral NDRG2 overexpression in BRL cells, flow cytometry, Western blotting for cell cycle regulators and apoptosis markers Wound repair and regeneration Low 20840522
2013 NDRG2 acts downstream of PI3K/Akt signaling in cardiomyocytes; insulin increases Akt-dependent NDRG2 phosphorylation, and shRNA knockdown of NDRG2 renders cardiomyocytes more susceptible to ischemia/reperfusion injury and blunts insulin's anti-apoptotic cardioprotective effect. Rat I/R model, lentiviral shRNA NDRG2 knockdown in cardiomyocytes and in vivo, Western blotting for phospho-Akt and phospho-NDRG2, wortmannin/Akt inhibitor pretreatment, infarct size measurement Basic research in cardiology Medium 23463182
2010 NDRG2 is highly expressed in pancreatic beta cells and acts as an Akt substrate; in beta cells under lipotoxic stress, Akt-mediated NDRG2 phosphorylation is reduced; NDRG2 knockdown attenuates constitutively active Akt-mediated protection against fatty acid-induced apoptosis, placing NDRG2 downstream of Akt in beta cell survival signaling. Stable overexpression of constitutively active Akt, NDRG2 knockdown in beta-TC3 cells, Western blotting, apoptosis assay Cellular and molecular life sciences Medium 20127388
2005 NDRG2 protein (both S and L isoforms) localizes specifically to cell surface membranes and growth cones in NGF-differentiated PC12 cells, and overexpression of either isoform promotes neurite elongation. V5-tagged NDRG2 transfection, immunofluorescence/confocal microscopy, real-time qPCR for expression, morphological measurement of neurite length Neuroscience letters Medium 16039777
2011 In cultured astrocytes, Ndrg2 gene silencing enhances cell proliferation (BrdU/PCNA incorporation) and reduces F-actin levels and process length, while Ndrg2 overexpression has opposite effects; fractionation and immunocytochemistry show Ndrg2 in cytosol and cell surface membrane fractions. Adenovirus-mediated Ndrg2 overexpression and siRNA knockdown in astrocytes, BrdU incorporation, PCNA staining, F-actin quantification, subcellular fractionation, MPTP mouse model Neurochemistry international Medium 21672576
2017 NDRG2 deficiency in Ndrg2-knockout mice leads to markedly increased interstitial glutamate and reduced astroglial glutamate clearance; an NDRG2 peptide rescues astroglial glutamate clearance, reduces excitatory transmission, and rescues ADHD-like hyperactivity in Ndrg2-/- mice. Ndrg2-knockout mice, microdialysis for interstitial glutamate, electrophysiology for excitatory transmission, astrocyte glutamate uptake assay, NDRG2 peptide treatment, behavioral testing The Journal of clinical investigation High 29058689
2021 NDRG2 overexpression in breast cancer cells inhibits PD-L1 expression through NF-κB signaling; knockdown of NDRG2 enhances PD-L1 expression and leads to suppression of T cell proliferation in co-culture, while NDRG2 overexpression in 4T1 mouse cells blocks tumor cell-mediated suppression of T cell proliferation. NDRG2 overexpression and knockdown, Western blotting, RT-qPCR, T cell proliferation co-culture assay, NF-κB pathway analysis Cancers Medium 34885221
2020 NDRG2 suppression in astrocytes attenuates ischemia-induced necroptosis by suppressing RIPK1 expression; Ndrg2-/- mice exhibit accelerated necroptosis after cerebral artery occlusion, and pharmacological inhibition of necroptosis by necrostatin-1 provides neuroprotection after NDRG2 knockdown. Ndrg2 conditional knockout mice, Western blotting for RIPK1 and necroptosis markers, necrostatin-1 treatment, permanent MCAO model Molecular medicine reports Medium 32945444
2022 Lactate stabilizes NDRG2 in astrocytes under oxygen-glucose deprivation by inhibiting its ubiquitination; NDRG2 knockdown in astrocytes increases TNFα expression and secretion via c-Jun phosphorylation, indicating that NDRG2 suppresses neuroinflammation by restraining the c-Jun/TNFα axis. Ubiquitination assay, Western blotting, siRNA knockdown, exogenous lactate treatment, RNA-seq transcriptomics, primary astrocyte culture, MCAO rat model Journal of neuroinflammation Medium 36572898
2012 Ndrg2 loss in mice results in vertebral homeotic transformations; at the molecular level, this is accompanied by altered Hoxc8-11 gene transcripts and elevated BMP/Smad signaling in differentiating somites, identifying Ndrg2 as a regulator of vertebral specification after somite segmentation. Ndrg2-knockout mice, conditional knockout in osteoblasts/chondrocytes, Ndrg2 overexpression in osteoblasts/chondrocytes, in situ hybridization for Hox genes, immunostaining for phospho-Smad Developmental biology Medium 22819676
2014 NDRG2 is predominantly localized to the cytosol of protoplasmic and fibrous astrocytes in mammalian brain, including fine distal processes but not Müller glia; NDRG2 is reduced in reactive astrocytes at a cortical lesion, suggesting its expression is specific to mature, non-reactive astrocytes. Immunohistochemistry and confocal immunofluorescence with astrocyte markers (GFAP, S100β, aquaporin-4, nestin, NG2) in multiple species (mouse, rat, tree shrew, marmoset, human), cortical lesion model Cell and tissue research Medium 24816982
2011 NDRG2 regulates CD24 expression in hepatocellular carcinoma cells; NDRG2 upregulation decreases CD24 expression and reduces cell adhesion, migration and invasion, while NDRG2 downregulation enhances CD24 expression and increases these behaviors. Adenovirus-mediated NDRG2 overexpression and siRNA knockdown in HCC cells, Western blotting, adhesion/migration/invasion assays, IHC correlation in 50 patient specimens BMC cancer Low 21676268

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. International journal of cancer 193 12845671
2014 Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers. Nature communications 139 24569712
2008 Functional and clinical evidence for NDRG2 as a candidate suppressor of liver cancer metastasis. Cancer research 118 18519680
2002 Characterization of rat NDRG2 (N-Myc downstream regulated gene 2), a novel early mineralocorticoid-specific induced gene. The Journal of biological chemistry 116 12072429
2004 NDRG2: a novel Alzheimer's disease associated protein. Neurobiology of disease 110 15207261
2008 NDRG2: a Myc-repressed gene involved in cancer and cell stress. Acta biochimica et biophysica Sinica 97 18604454
2006 The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter. The Journal of biological chemistry 82 17050536
2003 Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells. FEBS letters 82 14572661
2008 Frequent promoter hypermethylation and transcriptional downregulation of the NDRG2 gene at 14q11.2 in primary glioblastoma. International journal of cancer 81 18709645
2010 HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells. Experimental cell research 80 20206160
2015 Tumor suppressor NDRG2 inhibits glycolysis and glutaminolysis in colorectal cancer cells by repressing c-Myc expression. Oncotarget 79 26317652
2011 NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression. BMC cancer 79 21676268
2004 NDRG2 expression and mutation in human liver and pancreatic cancers. World journal of gastroenterology 78 15526377
2012 FXR controls the tumor suppressor NDRG2 and FXR agonists reduce liver tumor growth and metastasis in an orthotopic mouse xenograft model. PloS one 77 23056173
2022 Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage. Science advances 76 36179025
2014 The iron chelator Dp44mT inhibits hepatocellular carcinoma metastasis via N-Myc downstream-regulated gene 2 (NDRG2)/gp130/STAT3 pathway. Oncotarget 72 25261367
2009 Bone morphogenetic protein-4 induced by NDRG2 expression inhibits MMP-9 activity in breast cancer cells. Biochemical and biophysical research communications 70 19450561
2006 Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues. Cell and tissue research 70 16520977
2007 Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma. BMC cancer 69 17935612
2007 Expression of NDRG2 is related to tumor progression and survival of gastric cancer patients through Fas-mediated cell death. Experimental & molecular medicine 69 18160841
2004 Akt mediates insulin-stimulated phosphorylation of Ndrg2: evidence for cross-talk with protein kinase C theta. The Journal of biological chemistry 69 14985363
2009 NDRG2 suppresses cell proliferation through down-regulation of AP-1 activity in human colon carcinoma cells. International journal of cancer 66 18844221
2014 NDRG2 as a marker protein for brain astrocytes. Cell and tissue research 64 24816982
2009 NDRG2 expression decreases with tumor stages and regulates TCF/beta-catenin signaling in human colon carcinoma. Carcinogenesis 64 19237607
2016 Emerging role of N-myc downstream-regulated gene 2 (NDRG2) in cancer. Oncotarget 62 26506239
2005 Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells. Neuroscience letters 62 16039777
2007 SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells. Biochemical and biophysical research communications 61 17888401
2018 NDRG2 facilitates colorectal cancer differentiation through the regulation of Skp2-p21/p27 axis. Oncogene 57 29343851
2016 Clinical and pathological significance of N-Myc downstream-regulated gene 2 (NDRG2) in diverse human cancers. Apoptosis : an international journal on programmed cell death 57 27113371
2003 Ndrg2, a novel gene regulated by adrenal steroids and antidepressants, is highly expressed in astrocytes. Annals of the New York Academy of Sciences 57 14993068
2016 Death-associated protein kinase 1 phosphorylates NDRG2 and induces neuronal cell death. Cell death and differentiation 55 28141794
2011 NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. PloS one 54 22110735
2022 MiR-181a-5p facilitates proliferation, invasion, and glycolysis of breast cancer through NDRG2-mediated activation of PTEN/AKT pathway. Bioengineered 51 34951340
2009 NDRG2, a novel regulator of myoblast proliferation, is regulated by anabolic and catabolic factors. The Journal of physiology 51 19204049
2020 Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6/JAK2/STAT3 signaling in glioma. Cellular oncology (Dordrecht, Netherlands) 49 32207044
2017 KLF4 inhibits colorectal cancer cell proliferation dependent on NDRG2 signaling. Oncology reports 49 28656310
2023 ROS promote hyper-methylation of NDRG2 promoters in a DNMTS-dependent manner: Contributes to the progression of renal fibrosis. Redox biology 47 36989575
2017 Deficiency of tumor suppressor NDRG2 leads to attention deficit and hyperactive behavior. The Journal of clinical investigation 45 29058689
2010 NDRG2 is a candidate tumor-suppressor for oral squamous-cell carcinoma. Biochemical and biophysical research communications 45 20045673
2023 Reprogramming astrocytic NDRG2/NF-κB/C3 signaling restores the diabetes-associated cognitive dysfunction. EBioMedicine 44 37329577
2018 Loss of NDRG2 in liver microenvironment inhibits cancer liver metastasis by regulating tumor associate macrophages polarization. Cell death & disease 44 29445150
2022 Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions. Journal of neuroinflammation 41 36572898
2015 Loss of NDRG2 enhanced activation of the NF-κB pathway by PTEN and NIK phosphorylation for ATL and other cancer development. Scientific reports 41 26269411
2020 NDRG2 regulates adherens junction integrity to restrict colitis and tumourigenesis. EBioMedicine 39 33099085
2018 The MYB/miR-130a/NDRG2 axis modulates tumor proliferation and metastatic potential in salivary adenoid cystic carcinoma. Cell death & disease 39 30206227
2017 Loss of NDRG2 Expression Confers Oral Squamous Cell Carcinoma with Enhanced Metastatic Potential. Cancer research 39 28209617
2011 The effect of Ndrg2 expression on astroglial activation. Neurochemistry international 39 21672576
2008 Immunohistochemical detection of Ndrg2 in the mouse nervous system. Neuroreport 39 18520995
2016 N-Myc Downstream-Regulated Gene 2 (Ndrg2) Is Involved in Ischemia-Hypoxia-Induced Astrocyte Apoptosis: a Novel Target for Stroke Therapy. Molecular neurobiology 38 27154863
2019 NDRG2 Protects the Brain from Excitotoxicity by Facilitating Interstitial Glutamate Uptake. Translational stroke research 37 31250377
2011 Spatial-temporal expression of NDRG2 in rat brain after focal cerebral ischemia and reperfusion. Brain research 36 21241684
2011 Suppression of invasion and metastasis of prostate cancer cells by overexpression of NDRG2 gene. Cancer letters 36 21741166
2014 NDRG2 controls COX-2/PGE₂-mediated breast cancer cell migration and invasion. Molecules and cells 35 25256221
2010 Expression of NDRG2 in esophageal squamous cell carcinoma. Cancer science 34 20331630
2008 Expression of NDRG2 in clear cell renal cell carcinoma. Biological & pharmaceutical bulletin 34 18591767
2020 LncRNA RAD51-AS1/miR-29b/c-3p/NDRG2 crosstalk repressed proliferation, invasion and glycolysis of colorectal cancer. IUBMB life 32 33314669
2012 Inhibition of endothelial cell proliferation and tumor angiogenesis by up-regulating NDRG2 expression in breast cancer cells. PloS one 32 22393400
2006 The physical and functional interaction of NDRG2 with MSP58 in cells. Biochemical and biophysical research communications 32 17109818
2012 DNA methylation of NDRG2 in gastric cancer and its clinical significance. Digestive diseases and sciences 31 23010743
2007 (NDRG2) stimulates amiloride-sensitive Na+ currents in Xenopus laevis oocytes and fisher rat thyroid cells. The Journal of biological chemistry 31 17652085
2010 NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498. Journal of experimental & clinical cancer research : CR 30 20673333
2013 NDRG2: a newly identified mediator of insulin cardioprotection against myocardial ischemia-reperfusion injury. Basic research in cardiology 29 23463182
2005 Expression of Ndrg2 in the rat frontal cortex after antidepressant and electroconvulsive treatment. The international journal of neuropsychopharmacology 29 15769300
2005 Expression of androgen receptor and androgen regulation of NDRG2 in the rat renal collecting duct. Pflugers Archiv : European journal of physiology 29 16142456
2023 Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing. Nature communications 28 37550295
2019 Astrocyte-specific NDRG2 gene: functions in the brain and neurological diseases. Cellular and molecular life sciences : CMLS 28 31834421
2010 NDRG2 in rat liver regeneration: role in proliferation and apoptosis. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 27 20840522
2021 N-myc Downstream-Regulated Gene 2 (NDRG2) Function as a Positive Regulator of Apoptosis: A New Insight into NDRG2 as a Tumor Suppressor. Cells 26 34685629
2020 Astrocytic NDRG2 is critical in the maintenance of neuropathic pain. Brain, behavior, and immunity 26 32688030
2011 Dexamethasone indirectly induces Ndrg2 expression in rat astrocytes. Journal of neuroscience research 26 21928335
2019 Ganoderic acid A/DM-induced NDRG2 over-expression suppresses high-grade meningioma growth. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 25 31732915
2010 Variation of NDRG2 and c-Myc expression in rat heart during the acute stage of ischemia/reperfusion injury. Histochemistry and cell biology 25 21193923
2022 The Function of N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Negative Regulator in Tumor Cell Metastasis. International journal of molecular sciences 24 36012631
2020 UNC5B-AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2. Cell biology international 24 31903696
2010 NDRG2 is highly expressed in pancreatic beta cells and involved in protection against lipotoxicity. Cellular and molecular life sciences : CMLS 24 20127388
2020 Association between NDRG2/IL-6/STAT3 signaling pathway and diabetic retinopathy in rats. European review for medical and pharmacological sciences 23 32329820
2017 NDRG2 knockdown promotes fibrosis in renal tubular epithelial cells through TGF-β1/Smad3 pathway. Cell and tissue research 23 28646304
2014 Estrogen regulates the expression of Ndrg2 in astrocytes. Brain research 23 24796879
2014 Glioma Malignancy-Dependent NDRG2 Gene Methylation and Downregulation Correlates with Poor Patient Outcome. Journal of Cancer 23 24847385
2012 Ndrg2 regulates vertebral specification in differentiating somites. Developmental biology 23 22819676
2010 NDRG2-mediated Modulation of SOCS3 and STAT3 Activity Inhibits IL-10 Production. Immune network 23 21286383
2009 NDRG2 induced by oxidized LDL in macrophages antagonizes growth factor productions via selectively inhibiting ERK activation. Biochimica et biophysica acta 21 19815093
2021 NDRG2 Expression in Breast Cancer Cells Downregulates PD-L1 Expression and Restores T Cell Proliferation in Tumor-Coculture. Cancers 20 34885221
2018 NDRG2 suppresses proliferation, migration, invasion and epithelial-mesenchymal transition of esophageal cancer cells through regulating the AKT/XIAP signaling pathway. The international journal of biochemistry & cell biology 20 29530788
2020 NDRG2 attenuates ischemia-induced astrocyte necroptosis via the repression of RIPK1. Molecular medicine reports 19 32945444
2020 NDRG2 ablation reprograms metastatic cancer cells towards glutamine dependence via the induction of ASCT2. International journal of biological sciences 19 33162818
2019 Suppression of NDRG2 alleviates brain injury after intracerebral hemorrhage through mitigating astrocyte-drived glutamate neurotoxicity via NF-κB/GLT1 signaling. Brain research 19 31843625
2012 NDRG2 and PRA1 interact and synergistically inhibit T-cell factor/β-catenin signaling. FEBS letters 19 23068607
2018 NDRG2 mRNA levels and miR-28-5p and miR-650 activity in chronic lymphocytic leukemia. BMC cancer 18 30348117
2016 NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors. Anticancer research 18 26976975
2015 The loss of NDRG2 expression improves depressive behavior through increased phosphorylation of GSK3β. Cellular signalling 18 26208882
2015 NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. Biochemical and biophysical research communications 18 26631961
2018 Hypoxia promotes migration and invasion of gastric cancer cells by activating HIF-1α and inhibiting NDRG2 associated signaling pathway. European review for medical and pharmacological sciences 17 30556863
2017 Potential role of NDRG2 in reprogramming cancer metabolism and epithelial-to-mesenchymal transition. Histology and histopathology 17 29285747
2012 Suppression of MMP-9 activity by NDRG2 expression inhibits clear cell renal cell carcinoma invasion. Medical oncology (Northwood, London, England) 17 22692967
2010 NDRG2 expression regulates CD24 and metastatic potential of breast cancer cells. Asian Pacific journal of cancer prevention : APJCP 17 21338239
2023 Inhibition of PI3K/Akt/mTOR signaling by NDRG2 contributes to neuronal apoptosis and autophagy in ischemic stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 16 36652790
2021 Colorectal Cancer Cell Differentiation Is Dependent on the Repression of Aerobic Glycolysis by NDRG2-TXNIP Axis. Digestive diseases and sciences 16 34373985
2016 Epigenetic silencing of NDRG2 promotes colorectal cancer proliferation and invasion. Journal of gastroenterology and hepatology 16 26250123
2016 Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 16 27007654

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