Affinage

MTDH

Protein LYRIC · UniProt Q86UE4

Length
582 aa
Mass
63.8 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTDH/AEG-1 is a multifunctional scaffold protein that integrates transcriptional regulation, RNA metabolism, and signal transduction to promote oncogenesis, metastasis, chemoresistance, and immune evasion. As a type-1b membrane protein localized to the ER, nuclear envelope, and nucleolus (PMID:14980505), MTDH operates through structurally defined protein–protein interactions: it binds SND1 via an 11-residue peptide motif to stabilize SND1 and destabilize Tap1/2 mRNAs encoding antigen-presentation machinery, thereby suppressing anti-tumor immunity (PMID:25242325, PMID:35121988); it protects CBP from ubiquitin-mediated degradation to drive TWIST1 transcription and cancer stemness (PMID:26141861); it sequesters RXR to inhibit retinoid and lipid-metabolic nuclear receptor signaling (PMID:25125681, PMID:26070567); and it recruits USP10 to deubiquitinate PARP1 at K48-linked Lys425, promoting DNA repair and radioresistance (PMID:37838281). In the cytoplasm, MTDH functions as an RNA-binding protein that associates with RISC components and regulates mRNA stability and translation of targets including FANCD2/FANCI (PMID:22199357, PMID:31477281), with its activity modulated by palmitoylation at Cys-75 catalyzed by zDHHC6 (PMID:36276642) and by NF-κB pathway activation essential for hepatocarcinogenesis (PMID:25193383).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2004 High

    The basic identity and topology of MTDH were established: it is a type-1b transmembrane protein residing at the ER, nuclear envelope, and nucleolus, resolving its subcellular distribution and membrane orientation.

    Evidence Subcellular fractionation, immunostaining, and Northern blot in multiple cell types

    PMID:14980505

    Open questions at the time
    • Determinants of dynamic redistribution between ER, nuclear envelope, and nucleolus were not defined
    • Membrane topology model based on single study
  2. 2004 Medium

    MTDH was found to colocalize with tight junction proteins ZO-1 and occludin in polarized epithelial cells, suggesting a role in junction maturation rather than structural integrity.

    Evidence Immunolocalization during tight junction disruption and reformation in polarized epithelial cells

    PMID:15383321

    Open questions at the time
    • No direct biochemical interaction with ZO-1 demonstrated
    • Functional consequence of junction association not tested by loss-of-function
  3. 2008 Medium

    Identification of BCCIP as an MTDH-binding partner revealed a mechanism by which MTDH promotes proteasomal degradation of a tumor suppressor-associated protein.

    Evidence Yeast two-hybrid and co-immunoprecipitation with proteasome inhibitor rescue

    PMID:18440304

    Open questions at the time
    • Direct ubiquitination of BCCIP by MTDH-associated E3 ligase not identified
    • In vivo significance not tested
  4. 2009 High

    Mapping of three NLS motifs and identification of ubiquitin modification at NLS-2 established that MTDH localization is actively regulated and that its cytoplasmic retention involves ubiquitination, explaining how a single protein operates in multiple compartments.

    Evidence GFP-NLS fusion deletion constructs, immunoprecipitation, Western blotting

    PMID:19383828

    Open questions at the time
    • E3 ligase responsible for NLS-2 ubiquitination not identified at this stage
    • Ubiquitin chain type not determined
  5. 2009 High

    Discovery that nuclear MTDH binds the transcriptional repressor PLZF and displaces it from promoters established MTDH as a modulator of transcription factor access to chromatin.

    Evidence Yeast two-hybrid, reciprocal co-IP in mammalian cells, promoter-binding assays, co-localization with HDAC-containing nuclear bodies

    PMID:19648967

    Open questions at the time
    • Genome-wide targets of PLZF derepression by MTDH not characterized
    • Physiological relevance in non-cancer contexts unknown
  6. 2011 High

    Defining MTDH as a cytoplasmic RNA-binding protein that associates with RISC components and regulates mRNA translation and stress granule dynamics fundamentally expanded its functional repertoire beyond transcriptional regulation.

    Evidence Subcellular fractionation, co-IP with RNA-binding proteins, mRNA regulation and stress granule assays upon knockdown

    PMID:22199357

    Open questions at the time
    • Direct RNA-binding domain not mapped
    • Specificity of mRNA target selection unclear
    • Whether RISC association is direct or bridged by SND1 not resolved
  7. 2011 High

    MTDH was shown to repress EAAT2 transcription through a YY1–CBP axis, linking it to excitotoxic neuronal death and revealing its first non-cancer pathological function.

    Evidence Gain/loss-of-function in astrocytes and glioma cells, patient correlation, transcriptional reporter assays

    PMID:21852380

    Open questions at the time
    • Whether YY1 recruitment is via direct MTDH–YY1 interaction not resolved
    • Relevance to neurodegenerative disease in vivo not tested
  8. 2011 High

    MTDH was identified as a host factor incorporated into HIV-1 virions via interaction with Gag MA/NC domains, establishing a viral biology dimension.

    Evidence Affinity purification, co-IP, domain mapping, virion incorporation, viral protease cleavage

    PMID:21957284

    Open questions at the time
    • Functional consequence of MTDH incorporation for viral infectivity not determined
    • Whether MTDH affects HIV-1 assembly or entry not tested
  9. 2014 High

    The MTDH–SND1 interaction was structurally resolved at atomic resolution, identifying a two-tryptophan peptide motif in MTDH that inserts into an SND1 groove; disruption of this interface abolished tumorigenicity, validating it as a druggable cancer target.

    Evidence X-ray crystallography of MTDH–SND1 complex, tryptophan mutagenesis, in vivo tumor-initiating cell assays and mouse models

    PMID:24981741 PMID:25242325

    Open questions at the time
    • Structural basis for how SND1 binding connects to RISC activity not resolved
    • Whether other MTDH regions contribute to SND1 regulation beyond the 11-residue motif unknown
  10. 2014 High

    MTDH was shown to inhibit retinoid signaling by sequestering RXR in the cytoplasm and by activating ERK-mediated RXR phosphorylation, providing a mechanistic basis for its role in both oncogenesis and lipid metabolism.

    Evidence Co-IP, immunofluorescence, fractionation, kinase assays in transgenic and knockdown models; confirmed in enterocyte-specific knockout for lipid absorption

    PMID:25125681 PMID:26070567

    Open questions at the time
    • Direct binding site on RXR not mapped
    • Whether MTDH–RXR interaction is druggable not explored
  11. 2014 High

    Genetic knockout of MTDH in mice revealed its essential role in NF-κB activation in hepatocytes and macrophages, establishing it as a non-redundant signaling node for inflammation-driven hepatocarcinogenesis.

    Evidence Mtdh knockout mice, DEN-induced HCC model, NF-κB and STAT3 pathway analysis

    PMID:25193383

    Open questions at the time
    • Molecular mechanism by which MTDH activates IKK/NF-κB not fully defined
    • Whether NF-κB role is direct or mediated through SND1 unclear
  12. 2015 High

    MTDH was found to stabilize CBP by preventing its ubiquitin-mediated degradation, thereby licensing H3 acetylation at the TWIST1 promoter and cancer stem cell expansion — establishing a second epigenetic mechanism distinct from RXR sequestration.

    Evidence Co-IP of MTDH–CBP, ChIP for H3 acetylation, ubiquitination assays, CSC functional readouts

    PMID:26141861

    Open questions at the time
    • E3 ligase targeting CBP in this context not identified
    • Whether MTDH–CBP interaction is direct or scaffold-mediated unknown
  13. 2019 Medium

    MTDH's RNA-binding activity was shown to directly regulate FANCD2/FANCI mRNA stability, mechanistically linking MTDH to the Fanconi anemia DNA repair pathway and platinum chemoresistance.

    Evidence RNA immunoprecipitation confirming direct MTDH–mRNA binding, knockdown with chemosensitivity readout, patient-derived xenograft model

    PMID:31477281

    Open questions at the time
    • RNA-binding domain/motif in MTDH not defined
    • Whether regulation occurs through RISC or independent mechanism not distinguished
  14. 2021 High

    The MTDH–SND1 complex was shown to destabilize Tap1/2 mRNAs encoding antigen-presentation machinery, directly linking this interaction to tumor immune evasion; pharmacological disruption with C26-A6 restored T cell infiltration and synergized with anti-PD-1 therapy.

    Evidence Genetic and pharmacological MTDH–SND1 disruption, mRNA stability assays for Tap1/2, in vivo immune phenotyping in breast cancer models

    PMID:35121987 PMID:35121988

    Open questions at the time
    • Full spectrum of mRNAs destabilized by MTDH–SND1 not cataloged
    • Whether C26-A6 has off-target effects in immune cells not fully assessed
    • Clinical translation of MTDH–SND1 inhibitors not yet tested
  15. 2022 High

    Palmitoylation at Cys-75 by zDHHC6 (reversed by PPT1/2) was identified as a post-translational switch that destabilizes MTDH protein and weakens MTDH–SND1 binding, with Zdhhc6 knockout enhancing hepatocarcinogenesis — revealing lipid modification as a regulatory layer.

    Evidence Acyl-RAC assay, Cys-75 knock-in mice, Zdhhc6 knockout mice, DEN-induced HCC model

    PMID:36276642

    Open questions at the time
    • Structural basis for how Cys-75 palmitoylation disrupts SND1 binding not determined
    • Whether palmitoylation affects other MTDH interactions (CBP, RXR) not tested
  16. 2023 High

    MTDH was found to recruit USP10 to deubiquitinate K48-linked polyubiquitin at PARP1-Lys425, preventing PARP1 degradation and enabling homologous recombination repair — establishing a direct mechanism for MTDH-driven radioresistance.

    Evidence Co-IP, K48 linkage-specific ubiquitination assays, PARP1-K425R mutagenesis, γH2AX assays, xenograft irradiation models

    PMID:37838281

    Open questions at the time
    • Whether MTDH–USP10 interaction is direct or bridged not fully resolved
    • Generalizability beyond ESCC not tested
    • Whether other DNA repair substrates are regulated by MTDH–USP10 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for MTDH's RNA-binding specificity, the complete catalog of mRNA targets regulated through RISC, whether the NF-κB activation mechanism involves a direct molecular interaction with IKK complex components, and whether clinical-grade MTDH–SND1 inhibitors can achieve therapeutic efficacy in patients.
  • RNA-binding domain/motif in MTDH not structurally defined
  • Transcriptome-wide identification of MTDH-bound mRNAs incomplete
  • Direct versus indirect mechanism of NF-κB activation unresolved
  • No clinical trial data for MTDH-SND1 inhibitors

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005730 nucleolus 2 GO:0005635 nuclear envelope 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 1
Partners
BCCIPCBPGSK3BPARP1PLZFRXRSND1USP10
Complex memberships
MTDH-SND1 complexRISC

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 LYRIC/MTDH (also called 3D3/lyric) is a type-1b membrane protein with a single transmembrane domain, localized to the endoplasmic reticulum, nuclear envelope, and nucleolus, as determined by subcellular fractionation and immunostaining. Subcellular fractionation, immunostaining, Northern blot, antibody characterization Experimental cell research High 14980505
2004 LYRIC/MTDH colocalizes with tight junction proteins ZO-1 and occludin in polarized epithelial cells and dissociates from ZO-1 when junctional complexes are disrupted, indicating it is recruited during tight junction maturation rather than being a structural component. Immunolocalization of LYRIC with ZO-1 and occludin in polarized epithelial cells; disruption and reformation of tight junctions Experimental cell research Medium 15383321
2009 LYRIC/AEG-1 contains three nuclear localization signals (NLS): NLS-3 (aa 546–582) is the predominant regulator of nuclear localization, NLS-1 (aa 78–130) regulates nucleolar localization, and NLS-2 (aa 415–486) is the site of ubiquitin modification in the cytoplasm. GFP-NLS fusion proteins, deletion constructs, immunoprecipitation, Western blotting Clinical cancer research High 19383828
2009 Nuclear LYRIC/AEG-1 interacts with the transcriptional repressor PLZF via the N- and C-termini of LYRIC and the C-terminal region of PLZF (C-terminal to RD2 domain), and co-expression of LYRIC reduces PLZF binding to promoters, relieving PLZF-mediated repression; both proteins co-localize to nuclear bodies containing histone deacetylases. Yeast two-hybrid screen, co-immunoprecipitation in mammalian cells, promoter-binding assays, co-localization microscopy Oncogene High 19648967
2008 LYRIC/AEG-1 interacts with BCCIPα (a CDKN1A and BRCA2-associated protein) in mammalian cells; co-expression leads to decreased BCCIPα protein levels that is partially reversed by proteasome inhibition, indicating LYRIC promotes proteasomal degradation of BCCIPα. Yeast two-hybrid screen, co-immunoprecipitation, Western blotting with proteasome inhibitor Biochemical and biophysical research communications Medium 18440304
2011 AEG-1/MTDH represses the glutamate transporter EAAT2 at the transcriptional level by inducing YY1 activity to inhibit CBP function as a coactivator on the EAAT2 promoter, resulting in reduced glutamate uptake and neuronal cell death (excitotoxicity). Gain- and loss-of-function studies in primary human fetal astrocytes and T98G cells, Pearson correlation analysis in patient samples, transcriptional assays Cancer research High 21852380
2011 Cytoplasmic MTDH functions as an RNA-binding protein; it associates with RNA-binding proteins and components of the RNA-induced silencing complex (RISC) in a nucleic acid-dependent manner, regulates protein expression of multiple mRNAs (e.g., PDCD10, KDM6A), and its depletion leads to increased stress granule formation and reduced cell survival. Subcellular fractionation, co-immunoprecipitation with RNA-binding proteins, mRNA regulation assays, knockdown with stress granule and survival readouts The Journal of biological chemistry High 22199357
2014 MTDH interacts with and stabilizes SND1 (Staphylococcal nuclease domain-containing 1), supporting tumor-initiating cell survival under oncogenic/stress conditions; silencing MTDH or SND1 individually or disrupting their interaction compromises tumorigenicity in vivo. Mouse mammary tumor models, Co-IP, in vivo TIC assays, genetic silencing of MTDH and SND1 Cancer cell High 24981741
2014 The crystal structure of the MTDH-SND1 complex was determined at high resolution, revealing an 11-residue MTDH peptide motif occupying an extended protein groove between SN1/2 domains of SND1, with two MTDH tryptophan residues critical for the interaction; mutagenesis of these residues disrupts cancer-promoting activity and SND1 stability. X-ray crystallography, mutagenesis, in vitro and in vivo functional assays Cell reports High 25242325
2014 AEG-1/MTDH interacts with retinoid X receptor (RXR) in the nucleus of non-tumor cells, interfering with recruitment of transcriptional coactivators to RXR. In tumor cells, overexpressed AEG-1 sequesters RXR in the cytoplasm; additionally, ERK activated by AEG-1 phosphorylates RXR, causing its functional inactivation. Co-immunoprecipitation, immunofluorescence, nuclear/cytoplasmic fractionation, kinase assays, AEG-1 transgenic and knockdown models Cancer research High 25125681
2014 AEG-1 is essential for NF-κB activation in hepatocytes and macrophages; AEG-1-deficient mice show defective NF-κB signaling, reduced IL-6 production, and impaired STAT3 activation, conferring resistance to DEN-induced hepatocellular carcinoma. AEG-1 knockout mouse model, DEN-induced hepatocarcinogenesis, NF-κB and STAT3 pathway analysis Cancer research High 25193383
2015 MTDH promotes cancer stem-like cell expansion by interacting with the histone acetyltransferase CBP and preventing its ubiquitin-mediated degradation, thereby licensing CBP-mediated histone H3 acetylation on the TWIST1 promoter and activating TWIST1 transcription. Co-immunoprecipitation of MTDH-CBP, chromatin immunoprecipitation, ubiquitination assays, knockdown/overexpression with CSC phenotype readouts Cancer research High 26141861
2015 AEG-1 interacts with RXR and inhibits RXR-dependent activation of liver X receptor and PPARα in enterocytes, resulting in decreased intestinal fat absorption; AEG-1 knockout mice are leaner and resistant to high-fat diet-induced obesity. AEG-1 knockout mouse model, high-fat diet challenge, nuclear receptor activity assays The Journal of biological chemistry High 26070567
2013 CPEB1 binds the MTDH mRNA and represses its translation; phosphorylation of CPEB1 triggers cytoplasmic polyadenylation and translational activation of MTDH mRNA, promoting glioblastoma cell migration and tumor growth. RNA-binding assay, CPEB1 phosphorylation-deficient mutant, in vitro and in vivo tumor models, reporter mRNA localization Molecular cancer research Medium 23360795
2011 The cellular protein Lyric/MTDH interacts with HIV-1 Gag via the Gag matrix (MA) and nucleocapsid (NC) domains; this interaction requires Gag multimerization and Lyric amino acids 101–289; endogenous Lyric is incorporated into HIV-1 virions and cleaved by the viral protease. Affinity purification, co-immunoprecipitation, domain mapping, virion analysis, viral protease cleavage assay Journal of virology High 21957284
2016 AEG-1 activates Wnt/PCP-Rho signaling to promote EMT and invasion in tongue squamous cell carcinoma; recombinant AEG-1 activates Wnt5a/Rac1/ROCK pathway, and its stimulatory effects are reversed by anti-Wnt5a neutralizing antibody or inhibition of Rac1/ROCK. Recombinant AEG-1 treatment, neutralizing antibody, kinase inhibitors, xenograft model, EMT marker analysis Oncotarget Medium 26689985
2016 AEG-1 upregulates transcription of the membrane protein Tetraspanin 8 (TSPAN8), which mediates AEG-1-induced invasion, migration, and angiogenesis in hepatocellular carcinoma; TSPAN8 knockdown abolishes AEG-1-dependent metastasis in an orthotopic xenograft model. Gene expression analysis, TSPAN8 knockdown, invasion/migration assays, HUVEC tube formation, orthotopic xenograft in nude mice FEBS letters Medium 27339400
2017 AEG-1 promotes gastric cancer metastasis by positively regulating eIF4E expression, which in turn upregulates MMP-9 and Twist; manipulation of eIF4E partially rescues AEG-1-induced EMT, migration, and invasion. Gain/loss-of-function of AEG-1 and eIF4E, Western blotting, cell migration and invasion assays, orthotopic mouse model Journal of cellular and molecular medicine Medium 28661037
2018 LINC01638 interacts with c-Myc protein to prevent SPOP-mediated ubiquitination and degradation of c-Myc; stabilized c-Myc transcriptionally activates MTDH expression, which subsequently activates TWIST1, driving EMT in triple-negative breast cancer. RNA-protein interaction assay, ubiquitination assay, chromatin immunoprecipitation, knockdown/overexpression in TNBC cells and xenografts Oncogene High 30002443
2019 MTDH as an RNA-binding protein regulates the mRNA stability of FANCD2 and FANCI (Fanconi anemia complementation group proteins); RNA-binding protein immunoprecipitation confirmed direct MTDH-mRNA interaction, and MTDH knockdown reduced FANCD2/FANCI levels, restoring platinum sensitivity. RNA-binding protein immunoprecipitation (RIP), knockdown, chemosensitivity assays, patient-derived xenograft model Gynecologic oncology Medium 31477281
2020 CPEB3 binds the 3'-UTR of MTDH mRNA and suppresses its translation; CPEB3 knockout mice show increased susceptibility to carcinogen-induced hepatocarcinogenesis; CPEB3 overexpression inhibits EMT and metastasis of HCC cells by post-transcriptional suppression of MTDH. RNA immunoprecipitation (transcriptome-wide), luciferase assay with MTDH 3'-UTR, CPEB3 knockout mice, in vivo metastasis models Cell death & disease High 32968053
2021 The MTDH-SND1 complex binds to and destabilizes Tap1/2 mRNAs (encoding antigen-presentation machinery components), reducing tumor antigen presentation and inhibiting T cell infiltration; pharmacological disruption of MTDH-SND1 by compound C26-A6 restores immune surveillance and synergizes with anti-PD-1 therapy. Genetic and pharmacological disruption of MTDH-SND1 complex, mRNA stability assays for Tap1/2, in vivo preclinical breast cancer models, immune phenotyping Nature cancer High 35121988
2021 Genetic ablation of Mtdh in mice disrupts the MTDH-SND1 interaction and inhibits breast cancer development; small-molecule inhibitors C26-A2 and C26-A6 that disrupt the MTDH-SND1 protein-protein interaction suppress tumor growth and metastasis and enhance chemotherapy sensitivity in TNBC preclinical models. Genetically modified mouse models (Mtdh ablation), compound screening, in vivo TNBC models, chemosensitivity assays Nature cancer High 35121987
2022 AEG-1 undergoes palmitoylation on Cys-75, catalyzed by zDHHC6 and reversed by PPT1/2; palmitoylation adversely regulates AEG-1 protein stability and weakens AEG-1-SND1 interaction, thereby altering RISC activity and expression of tumor suppressors; blocking palmitoylation via Zdhhc6 knockout enhances DEN-induced HCC progression in vivo. Acyl-RAC assay, Cys-75 point mutation (AEG-1-C75A knock-in mice), Zdhhc6 knockout mice, DEN-induced HCC model, biochemical interaction assays Theranostics High 36276642
2023 AEG-1 promotes radioresistance in ESCC by recruiting the deubiquitinase USP10 to remove K48-linked polyubiquitin chains at Lys425 of PARP1, preventing its proteasomal degradation and thereby facilitating homologous recombination-mediated DNA double-strand break repair. Co-immunoprecipitation, ubiquitination assays with K48 linkage specificity, PARP1 mutagenesis (Lys425), DNA damage (γH2AX) assays, in vivo xenograft irradiation models Cancer letters High 37838281
2022 DOT1L, a H3K79 methyltransferase, promotes MTDH transcription by increasing H3K79me3 levels on the MTDH promoter as shown by ChIP; MTDH in turn activates NF-κB occupancy on the HIF1α promoter, leading to elevated proangiogenic mediators in TNBC cells. ChIP assay for H3K79me3 on MTDH promoter, DOT1L inhibitor/siRNA, NF-κB ChIP on HIF1α promoter, angiogenesis assays in vitro and in vivo The FEBS journal Medium 36017623
2018 FBXW7, an E3 ubiquitin ligase component, targets MTDH for ubiquitin-mediated proteasomal degradation; FBXW7 overexpression decreases MTDH protein levels and induces proliferation arrest and apoptosis in breast cancer cells. FBXW7 overexpression and knockdown, Western blotting, proliferation and apoptosis assays Neoplasma Medium 29534580
2014 MTDH mediates trastuzumab resistance in HER2-positive breast cancer by activating IκBα inhibition and nuclear translocation of NF-κB p65, which subsequently decreases PTEN expression; forced PTEN expression restores trastuzumab sensitivity. MTDH knockdown and overexpression, NF-κB pathway analysis, PTEN rescue experiments, in vivo xenograft models BMC cancer Medium 25417825
2021 MTDH acts as an RNA-binding protein that directly binds circ-NOL10 (with characterized RBP motifs), and ectopic expression or depletion of MTDH leads to circ-NOL10 expression changes, indicating MTDH modulates circRNA biogenesis or stability. RNA immunoprecipitation, RBP motif characterization, overexpression/knockdown of MTDH with circ-NOL10 readout Molecular therapy. Nucleic acids Low 34729247
2021 AEG-1 activates Wnt/β-catenin signaling by directly interacting with GSK-3β in the cytoplasm of glioma cells, as shown by co-immunoprecipitation and immunofluorescence co-localization. Co-immunoprecipitation, immunofluorescence co-localization, Western blot for β-catenin pathway components Scientific reports Medium 34462446

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The multifaceted role of MTDH/AEG-1 in cancer progression. Clinical cancer research : an official journal of the American Association for Cancer Research 231 19723648
2010 Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer. Carcinogenesis 185 20952513
2018 Long noncoding RNA SNHG1 promotes non-small cell lung cancer progression by up-regulating MTDH via sponging miR-145-5p. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 123 29466052
2014 MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors. Cancer cell 118 24981741
2012 MiR-136 promotes apoptosis of glioma cells by targeting AEG-1 and Bcl-2. FEBS letters 116 22967897
2011 Astrocyte elevated gene-1 (AEG-1): A multifunctional regulator of normal and abnormal physiology. Pharmacology & therapeutics 113 21256156
2018 LINC01638 lncRNA activates MTDH-Twist1 signaling by preventing SPOP-mediated c-Myc degradation in triple-negative breast cancer. Oncogene 110 30002443
2011 Oncogene AEG-1 promotes glioma-induced neurodegeneration by increasing glutamate excitotoxicity. Cancer research 99 21852380
2004 Identification of a novel protein, LYRIC, localized to tight junctions of polarized epithelial cells. Experimental cell research 96 15383321
2013 AEG-1/MTDH/LYRIC: signaling pathways, downstream genes, interacting proteins, and regulation of tumor angiogenesis. Advances in cancer research 86 23889988
2004 3D3/lyric: a novel transmembrane protein of the endoplasmic reticulum and nuclear envelope, which is also present in the nucleolus. Experimental cell research 86 14980505
2015 Epigenetic Activation of TWIST1 by MTDH Promotes Cancer Stem-like Cell Traits in Breast Cancer. Cancer research 83 26141861
2009 LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation and intrinsic nuclear localization signals. Clinical cancer research : an official journal of the American Association for Cancer Research 76 19383828
2016 Dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p) coordinately targeted MTDH in lung squamous cell carcinoma. Oncotarget 73 27765924
2013 AEG-1/MTDH/LYRIC: clinical significance. Advances in cancer research 73 23889987
2015 The role of MTDH/AEG-1 in the progression of cancer. International journal of clinical and experimental medicine 70 26131054
2021 Long non-coding RNA NORAD/miR-224-3p/MTDH axis contributes to CDDP resistance of esophageal squamous cell carcinoma by promoting nuclear accumulation of β-catenin. Molecular cancer 69 34893064
2021 LncRNA OTUD6B-AS1 promotes paclitaxel resistance in triple negative breast cancer by regulation of miR-26a-5p/MTDH pathway-mediated autophagy and genomic instability. Aging 62 34740994
2009 Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression. Oncogene 60 19648967
2021 Pharmacological disruption of the MTDH-SND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer. Nature cancer 58 35121988
2008 LYRIC/AEG-1 overexpression modulates BCCIPalpha protein levels in prostate tumor cells. Biochemical and biophysical research communications 57 18440304
2014 Genetic deletion of AEG-1 prevents hepatocarcinogenesis. Cancer research 54 25193383
2013 Drug resistance mediated by AEG-1/MTDH/LYRIC. Advances in cancer research 54 23889990
2014 AEG-1 3'-untranslated region functions as a ceRNA in inducing epithelial-mesenchymal transition of human non-small cell lung cancer by regulating miR-30a activity. European journal of cell biology 53 25484183
2013 miR-137 suppresses cell growth in ovarian cancer by targeting AEG-1. Biochemical and biophysical research communications 53 24144591
2021 Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis. Nature cancer 52 35121987
2013 AEG-1/MTDH/LYRIC in liver cancer. Advances in cancer research 52 23889992
2011 Cytoplasmic Metadherin (MTDH) provides survival advantage under conditions of stress by acting as RNA-binding protein. The Journal of biological chemistry 52 22199357
2018 Huaier Granule extract inhibit the proliferation and metastasis of lung cancer cells through down-regulation of MTDH, JAK2/STAT3 and MAPK signaling pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 51 29499405
2015 Downregulated AEG-1 together with inhibited PI3K/Akt pathway is associated with reduced viability of motor neurons in an ALS model. Molecular and cellular neurosciences 51 26320681
2019 Micheliolide ameliorates diabetic kidney disease by inhibiting Mtdh-mediated renal inflammation in type 2 diabetic db/db mice. Pharmacological research 45 31669149
2018 miR-145 and miR-497 suppress TGF-β-induced epithelial-mesenchymal transition of non-small cell lung cancer by targeting MTDH. Cancer cell international 45 30065618
2022 Breast cancer derived exosomes promoted angiogenesis of endothelial cells in microenvironment via circHIPK3/miR-124-3p/MTDH axis. Cellular signalling 44 35460835
2019 MiR-182-5p inhibited proliferation and metastasis of colorectal cancer by targeting MTDH. European review for medical and pharmacological sciences 44 30840271
2017 Hypoxia-inducible factor 1a induces phenotype switch of human aortic vascular smooth muscle cell through PI3K/AKT/AEG-1 signaling. Oncotarget 44 28415624
2014 AEG-1 regulates retinoid X receptor and inhibits retinoid signaling. Cancer research 44 25125681
2011 AEG -1 overexpression: a novel indicator for peritoneal dissemination and lymph node metastasis in epithelial ovarian cancers. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 44 21543927
2016 A polysaccharide from Huaier induced apoptosis in MCF-7 breast cancer cells via down-regulation of MTDH protein. Carbohydrate polymers 42 27474651
2016 AEG-1/MTDH-activated autophagy enhances human malignant glioma susceptibility to TGF-β1-triggered epithelial-mesenchymal transition. Oncotarget 40 26909607
2014 Structural insights into the tumor-promoting function of the MTDH-SND1 complex. Cell reports 40 25242325
2011 MTDH/AEG-1-based DNA vaccine suppresses lung metastasis and enhances chemosensitivity to doxorubicin in breast cancer. Cancer immunology, immunotherapy : CII 40 21400023
2014 MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway. BMC cancer 39 25417825
2013 CPEB1 regulates the expression of MTDH/AEG-1 and glioblastoma cell migration. Molecular cancer research : MCR 38 23360795
2019 circMTDH.4/miR-630/AEG-1 axis participates in the regulation of proliferation, migration, invasion, chemoresistance, and radioresistance of NSCLC. Molecular carcinogenesis 36 31749230
2022 The palmitoylation of AEG-1 dynamically modulates the progression of hepatocellular carcinoma. Theranostics 35 36276642
2017 miR-217 suppresses proliferation, migration, and invasion promoting apoptosis via targeting MTDH in hepatocellular carcinoma. Oncology reports 35 28184926
2014 MTDH mediates estrogen-independent growth and tamoxifen resistance by down-regulating PTEN in MCF-7 breast cancer cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 24854844
2019 Dysregulation of miR-375/AEG-1 Axis by Human Papillomavirus 16/18-E6/E7 Promotes Cellular Proliferation, Migration, and Invasion in Cervical Cancer. Frontiers in oncology 34 31552174
2016 AEG-1/MTDH/LYRIC: A Promiscuous Protein Partner Critical in Cancer, Obesity, and CNS Diseases. Advances in cancer research 34 27451125
2013 Pleiotropic roles of AEG-1/MTDH/LYRIC in breast cancer. Advances in cancer research 34 23889989
2019 Activation of EMT in colorectal cancer by MTDH/NF-κB p65 pathway. Molecular and cellular biochemistry 33 30825051
2014 AEG-1 promotes anoikis resistance and orientation chemotaxis in hepatocellular carcinoma cells. PloS one 33 24941119
2020 CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression. Cell death & disease 32 32968053
2019 Micheliolide ameliorates renal fibrosis by suppressing the Mtdh/BMP/MAPK pathway. Laboratory investigation; a journal of technical methods and pathology 32 30976056
2021 Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance. Cancers 31 33918653
2015 Downregulation of miR-375 in aldosterone-producing adenomas promotes tumour cell growth via MTDH. Clinical endocrinology 31 25944465
2018 MiR-136 triggers apoptosis in human gastric cancer cells by targeting AEG-1 and BCL2. European review for medical and pharmacological sciences 30 30468468
2017 miR-195 inhibits cell proliferation via targeting AEG-1 in hepatocellular carcinoma. Oncology letters 30 28529562
2019 miR‑3664‑5P suppresses the proliferation and metastasis of gastric cancer by attenuating the NF‑κB signaling pathway through targeting MTDH. International journal of oncology 29 30628643
2018 Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective osteosarcoma therapy. International journal of nanomedicine 29 29467575
2013 The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease. Advances in cancer research 29 23889991
2017 MiR-98 inhibits malignant progression via targeting MTDH in squamous cell carcinoma of the head and neck. American journal of cancer research 28 29312808
2015 Apoptosis of human non-small-cell lung cancer A549 cells triggered by evodiamine through MTDH-dependent signaling pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 28 25652471
2012 Clinical implications of AEG-1 in liver metastasis of colorectal cancer. Medical oncology (Northwood, London, England) 27 22351252
2023 The AEG-1-USP10-PARP1 axis confers radioresistance in esophageal squamous cell carcinoma via facilitating homologous recombination-dependent DNA damage repair. Cancer letters 26 37838281
2018 The FBXW7 tumor suppressor inhibits breast cancer proliferation and promotes apoptosis by targeting MTDH for degradation. Neoplasma 26 29534580
2017 MicroRNA-154 inhibits the growth and metastasis of gastric cancer cells by directly targeting MTDH. Oncology letters 26 28927076
2014 AEG-1 Promotes Metastasis Through Downstream AKR1C2 and NF1 in Liver Cancer. Oncology research 26 26351209
2018 MiR-1297 suppresses pancreatic cancer cell proliferation and metastasis by targeting MTDH. Molecular and cellular probes 25 29908229
2016 The Universal 3D3 Antibody of Human PODXL Is Pluripotent Cytotoxic, and Identifies a Residual Population After Extended Differentiation of Pluripotent Stem Cells. Stem cells and development 25 26886504
2016 Tetraspanin 8 mediates AEG-1-induced invasion and metastasis in hepatocellular carcinoma cells. FEBS letters 25 27339400
2015 MiR-302c-3p suppresses invasion and proliferation of glioma cells via down-regulating metadherin (MTDH) expression. Cancer biology & therapy 25 26176806
2016 AEG-1 activates Wnt/PCP signaling to promote metastasis in tongue squamous cell carcinoma. Oncotarget 24 26689985
2015 Astrocyte Elevated Gene-1 (AEG-1) Regulates Lipid Homeostasis. The Journal of biological chemistry 24 26070567
2014 MTDH/AEG-1 contributes to central features of the neoplastic phenotype in bladder cancer. Urologic oncology 24 24495449
2017 AEG-1 induces gastric cancer metastasis by upregulation of eIF4E expression. Journal of cellular and molecular medicine 23 28661037
2011 The cellular protein lyric interacts with HIV-1 Gag. Journal of virology 23 21957284
2021 Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review. Cells 22 34203598
2017 Novel Thiosemicarbazones Inhibit Lysine-Rich Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1) Coisolated (LYRIC) and the LYRIC-Induced Epithelial-Mesenchymal Transition via Upregulation of N-Myc Downstream-Regulated Gene 1 (NDRG1). Molecular pharmacology 22 28275050
2017 MicroRNA‑30a‑5p suppresses tumor cell proliferation of human renal cancer via the MTDH/PTEN/AKT pathway. International journal of molecular medicine 22 29207012
2016 Astrocyte elevated gene-1 (AEG-1) and the A(E)Ging HIV/AIDS-HAND. Progress in neurobiology 22 27090750
2012 Serum anti-AEG-1 auto-antibody is a potential novel biomarker for malignant tumors. Oncology letters 22 22844377
2021 MiR-9-3p regulates the biological functions and drug resistance of gemcitabine-treated breast cancer cells and affects tumor growth through targeting MTDH. Cell death & disease 21 34552061
2017 Down-regulated miR-26a promotes proliferation, migration, and invasion via negative regulation of MTDH in esophageal squamous cell carcinoma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 28174206
2021 AEG-1 silencing attenuates M2-polarization of glioma-associated microglia/macrophages and sensitizes glioma cells to temozolomide. Scientific reports 20 34462446
2021 Metadherin (AEG-1/MTDH/LYRIC) expression: Significance in malignancy and crucial role in colorectal cancer. Advances in clinical chemistry 20 35152973
2019 3D-3 Tumor Models in Drug Discovery for Analysis of Immune Cell Infiltration. Methods in molecular biology (Clifton, N.J.) 20 30912021
2019 microRNA-877 inhibits malignant progression of colorectal cancer by directly targeting MTDH and regulating the PTEN/Akt pathway. Cancer management and research 20 31114332
2019 MTDH/AEG-1 downregulation using pristimerin-loaded nanoparticles inhibits Fanconi anemia proteins and increases sensitivity to platinum-based chemotherapy. Gynecologic oncology 20 31477281
2015 Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin. PloS one 20 25993398
2021 The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review. Genes 19 33671513
2021 Circular RNA circHIPK3 modulates prostate cancer progression via targeting miR-448/MTDH signaling. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 19 34142340
2021 circ-NOL10 regulated by MTDH/CASC3 inhibits breast cancer progression and metastasis via multiple miRNAs and PDCD4. Molecular therapy. Nucleic acids 19 34729247
2022 DOT1L regulates MTDH-mediated angiogenesis in triple-negative breast cancer: intermediacy of NF-κB-HIF1α axis. The FEBS journal 18 36017623
2021 Downregulation of Long Noncoding RNA TUG1 Attenuates MTDH-Mediated Inflammatory Damage via Targeting miR-29b-1-5p After Spinal Cord Ischemia Reperfusion. Journal of neuropathology and experimental neurology 18 33225366
2019 AEG-1/miR-221 Axis Cooperatively Regulates the Progression of Hepatocellular Carcinoma by Targeting PTEN/PI3K/AKT Signaling Pathway. International journal of molecular sciences 18 31698701
2018 AEG-1 Contributes to Metastasis in Hypoxia-Related Ovarian Cancer by Modulating the HIF-1alpha/NF-kappaB/VEGF Pathway. BioMed research international 18 29770329
2018 Serum miR-30d as a novel biomarker for multiple myeloma and its antitumor role in U266 cells through the targeting of the MTDH/PI3K/Akt signaling pathway. International journal of oncology 18 30132507
2017 miR‑96 inhibits EMT by targeting AEG‑1 in glioblastoma cancer cells. Molecular medicine reports 18 29257267
2015 The role of AEG-1 in the development of liver cancer. Hepatic oncology 18 26798451