Affinage

MTX1

Metaxin-1 · UniProt Q13505

Round 2 corrected
Length
466 aa
Mass
51.5 kDa
Annotated
2026-04-29
130 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTX1 (Metaxin-1) is a mitochondrial outer membrane protein that functions as a component of the protein import and assembly machinery for beta-barrel proteins such as VDAC and Tom40, operating in concert with SAM50 and metaxin-2 (PMID:9045676, PMID:17510655). MTX1 is anchored via a C-terminal transmembrane domain with its N-terminus facing the cytosol, and it assembles into the MIB (mitochondrial intermembrane space bridging) supercomplex that bridges the outer and inner mitochondrial membranes alongside MICOS subunits, SAM50, MTX2, MTX3, CHCHD3/6, and DnaJC11 (PMID:17624330, PMID:26477565). MTX1 is a substrate of LC3C/p62-dependent piecemeal mitophagy, linking it to mitochondrial quality control (PMID:29149599). MTX1 overexpression promotes autophagy by interacting with and inhibiting the autophagy suppressor CISD1, contributing to sorafenib resistance in hepatocellular carcinoma (PMID:34421355).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1996 High

    Determining the genomic organization of MTX1 established its gene structure (eight exons, 317-amino-acid product) and revealed its convergent transcription with THBS3 and co-duplication with GBA, providing the foundation for all subsequent functional studies.

    Evidence Genomic sequencing, exon mapping, and Northern blot in human tissues

    PMID:8660965

    Open questions at the time
    • No functional data on the encoded protein at this stage
    • Pseudogene (psMTX) function unknown
  2. 1997 High

    Establishing that MTX1 is a mitochondrial outer membrane protein with a cytosol-exposed N-terminus that participates in preprotein import answered the fundamental question of where and how metaxin-1 functions, distinguishing it from its yeast homolog Tom37.

    Evidence Immunofluorescence in COS cells, protease protection on intact mitochondria, anti-metaxin antibody inhibition of preadrenodoxin import in vitro, C-terminal truncation mutagenesis

    PMID:9045676

    Open questions at the time
    • Only one substrate (preadrenodoxin) tested; specificity for beta-barrel vs. matrix-targeted precursors not resolved
    • Antibody inhibition is indirect — does not prove a direct receptor role
  3. 2005 Medium

    Linking MTX1-containing complexes to the SAM-dependent assembly pathway for Tom40 narrowed MTX1's import role to beta-barrel protein biogenesis rather than general matrix import.

    Evidence In vitro import of radiolabeled Tom40, blue native PAGE intermediate analysis, Sam50 RNAi in human cells

    PMID:15644312

    Open questions at the time
    • MTX1's role inferred from complex membership rather than direct depletion of MTX1 itself
    • Structural basis for MTX1 participation in SAM complex not determined
  4. 2007 High

    Functional RNAi experiments and immunocapture proteomics independently established that MTX1, metaxin-2, and SAM50 are interdependent components of a membrane-bridging complex (with mitofilin, CHCHD3/6, DnaJC11) required specifically for beta-barrel protein assembly, resolving the substrate specificity question.

    Evidence Metaxin-2 and Sam50 RNAi with radiolabeled VDAC/Tom40 import assays; anti-mitofilin immunocapture followed by mass spectrometry

    PMID:17510655 PMID:17624330

    Open questions at the time
    • Direct MTX1 depletion effects on import not shown (only metaxin-2 and Sam50 depleted)
    • Stoichiometry and subunit contacts within the complex undefined
  5. 2015 Medium

    Complexome profiling resolved MTX1's position within the MIB supercomplex hierarchy, showing it associates specifically with the fully assembled MIB (form C) rather than intermediate subcomplexes, clarifying its late-stage assembly role.

    Evidence Mitochondrial protein complexome profiling with blue native PAGE and evolutionary distribution analysis

    PMID:26477565

    Open questions at the time
    • Functional consequence of MTX1 absence from intermediate subcomplexes not tested
    • No reconstitution of MIB assembly in vitro
  6. 2017 Medium

    Identification of MTX1 as a cargo of LC3C/p62-dependent piecemeal mitophagy revealed that the outer membrane import machinery itself is subject to selective autophagic quality control, expanding MTX1's biology beyond import.

    Evidence BioID proximity labeling on autophagosomal markers combined with quantitative proteomics

    PMID:29149599

    Open questions at the time
    • Whether MTX1 degradation by piecemeal mitophagy has functional consequences for import capacity is untested
    • Signals targeting MTX1 for autophagic degradation not identified
  7. 2021 Medium

    A CRISPRa screen and follow-up experiments demonstrated a gain-of-function role for MTX1 in promoting autophagy through inhibition of CISD1, providing a mechanism for sorafenib resistance in hepatocellular carcinoma and revealing a non-import function for MTX1.

    Evidence Genome-scale CRISPRa screen, overexpression/knockdown in HCC cells, xenograft models, co-immunoprecipitation of MTX1-CISD1, autophagy flux assays

    PMID:34421355

    Open questions at the time
    • MTX1-CISD1 interaction demonstrated by single co-immunoprecipitation without reciprocal validation or domain mapping
    • Whether this autophagy-promoting role operates in non-cancer contexts is unknown
    • Mechanism by which MTX1 binding inhibits CISD1 function not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the direct structural contacts of MTX1 within the MIB/SAM complex, the phenotypic consequences of direct MTX1 loss-of-function on mitochondrial import in vivo, and whether MTX1's import and autophagy-related functions are mechanistically coupled.
  • No structure of MTX1 or its interfaces with SAM50/MTX2
  • No MTX1 knockout or conditional KO phenotype in animal models reported in this timeline
  • Relationship between import function and CISD1-mediated autophagy promotion unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-9609507 Protein localization 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-9612973 Autophagy 2
Partners
CHCHD3CHCHD6CISD1DNAJC11MTX2MTX3SAM50
Complex memberships
MIB (mitochondrial intermembrane space bridging) complexSAM complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Metaxin 1 (MTX1) is a mitochondrial outer membrane protein anchored via a C-terminal transmembrane domain with its N-terminal region exposed to the cytosol. Anti-metaxin antibodies partially inhibited import of radiolabeled preadrenodoxin into mitochondria, establishing MTX1 as a component of the mitochondrial preprotein import machinery of the outer membrane. MTX1 shows sequence similarity to yeast Tom37 but with distinct targeting mechanisms. Immunofluorescence localization in COS cells, protease protection assay on intact mitochondria, antibody inhibition of in vitro protein import, C-terminal truncation mutagenesis The Journal of Biological Chemistry High 9045676
1996 The human MTX1 gene spans 6 kb with eight protein-coding exons and encodes a 317-amino acid protein (91.5% identical to mouse metaxin). MTX1 is contiguous to THBS3 (sharing a common promoter, transcribed convergently) and adjacent to the glucocerebrosidase pseudogene (psGBA). The predicted protein lacks an N-terminal signal sequence but contains a putative C-terminal transmembrane domain. A pseudogene (psMTX) was identified within the GBA/psGBA region, containing a 278-amino acid ORF 97.8% identical to metaxin but lacking the first intron and promoter and not expressed in liver. Genomic sequencing, exon mapping, Northern blotting, sequence analysis Genomics High 8660965
1997 MTX1 (metaxin) was identified immediately downstream of the glucocerebrosidase pseudogene (psGBA) on chromosome 1q21. The genomic organization of the 75-kb region revealed that the duplication giving rise to psGBA also produced a pseudogene for MTX1, establishing MTX1's chromosomal context and its co-duplication with GBA. Genomic sequencing, restriction mapping, gene identification Genome Research Medium 9331372
2007 MTX1 (metaxin 1) exists in a high-molecular-weight complex with mitofilin (inner membrane), metaxin 2, SAM50, CHCHD3, CHCHD6, and DnaJC11, as revealed by immunocapture with an anti-mitofilin monoclonal antibody followed by mass spectrometry. This complex bridges the inner and outer mitochondrial membranes and likely functions in protein import and maintenance of mitochondrial structure. Monoclonal antibody immunocapture, SDS-PAGE, mass spectrometry identification of co-purifying proteins FEBS Letters High 17624330
2007 Depletion of metaxin 2 by RNAi caused reduction of metaxin 1 (MTX1) steady-state levels and deficient import and assembly of VDAC and Tom40 (but not matrix-targeted precursors), placing MTX1 in the pathway of beta-barrel protein biogenesis at the mitochondrial outer membrane. Reduction of Sam50 also led to decreased levels of both metaxin 1 and metaxin 2, indicating interdependence among Sam50, MTX1, and metaxin 2. RNAi knockdown, in vitro mitochondrial import assay with radiolabeled precursors, immunoblotting for steady-state levels EMBO Reports High 17510655
2005 Human Tom40 import involves the TOM complex as a first stable intermediate on the outer face, followed by membrane integration; metaxins (including MTX1) constitute part of the mammalian SAM complex through which Tom40 assembly is routed. Depletion of human Sam50 reduces Tom40 assembly, linking MTX1-containing complexes to the beta-barrel assembly pathway. In vitro import assay with radiolabeled Tom40 precursor, blue native PAGE to detect import intermediates, RNAi depletion of Sam50 The Journal of Biological Chemistry Medium 15644312
2011 MTX1 (metaxin 1) was identified as a component of mitofilin/MINOS complexes in human mitochondria by proteomic analyses. Disruption of MINOS1 affects mitochondrial morphology and inner membrane organization, and MTX1-containing complexes bridge inner and outer membranes. Co-immunoprecipitation, mass spectrometry proteomics of mitofilin complexes, electron microscopy of mitochondrial ultrastructure Molecular Biology of the Cell Medium 22114354
2015 Systematic analysis of the MICOS/MIB complex revealed that MTX1 is a component of the complete MIB (mitochondrial intermembrane space bridging) complex (form C), which also contains all MICOS proteins, SAMM50, MTX2, MTX3, and DNAJC11. MTX1 is distinguished from MTX2 and MTX3 in that it associates specifically with the fully assembled MIB complex rather than the membrane-bridging subcomplex. Mitochondrial protein complexome profiling, blue native PAGE, evolutionary distribution analysis across species Biochimica et Biophysica Acta Medium 26477565
2016 Affinity enrichment mass spectrometry of 50 mitochondrial proteins identified MTX1 as part of the mitochondrial interactome, confirming its association with the outer membrane import and assembly machinery. MTX1 interactions were catalogued as part of a network connecting diverse mitochondrial processes including respiratory chain function. Affinity enrichment mass spectrometry (AP-MS) of 50 mitochondrial bait proteins Molecular Cell Medium 27499296
2020 BioID proximity labeling using 100 mitochondrial baits (including outer membrane markers) identified MTX1 proximity interactions in the human mitochondrial outer membrane neighborhood. MTX1 showed proximity to proteins at the interface between the mitochondrial outer membrane and the endoplasmic reticulum, relevant to mitochondrial homeostasis. BioID proximity-dependent biotinylation with 100 mitochondrial bait proteins, mass spectrometry Cell Metabolism Medium 32877691
2017 LC3C- and p62-dependent piecemeal mitophagy involves the autophagic degradation of individual mitochondrial proteins including components of the outer membrane. Autophagosomal content profiling identified MTX1 among mitochondrial outer membrane proteins subject to selective autophagic degradation, implicating MTX1 in mitochondrial quality control via piecemeal mitophagy. Proximity labeling (BioID on autophagosomal markers) combined with quantitative proteomics to profile autophagosome contents Molecular Cell Medium 29149599
2011 The MTX1 c.184T>A (p.S63T) variant was found in 93% of GBA mutation carriers (PD patients and healthy controls) versus 64% of non-carriers (p=0.0008). Homozygosity for the MTX1 c.184A/A genotype was associated with significantly earlier age of motor symptom onset in GBA-associated Parkinson's disease patients (5.1–5.9 years younger, p=0.002–0.01), and higher frequency of early-onset PD (<50 years) in GBA+MTX1 homozygous carriers (35.9% vs 13.6–17.5%, p=0.028). The c.184A allele is in strong linkage disequilibrium with the GBA p.N370S mutation. Sequencing of entire MTX1 coding region and exon-intron boundaries in 81 PD-GBA carriers and controls; population genotyping of 600 PD patients and 353 controls; statistical association analysis Neurogenetics Medium 21837367
2021 Genome-scale CRISPRa screening identified MTX1 (Metaxin 1) as a contributor to sorafenib resistance in hepatocellular carcinoma (HCC). MTX1 overexpression promoted HCC cell proliferation in vitro and in vivo, decreased apoptosis upon sorafenib treatment, and enhanced autophagy. Mechanistically, MTX1 overexpression promoted autophagy by interacting with and inhibiting CISD1 (CDGSH iron sulfur domain 1, an autophagy negative regulator), as shown by co-immunoprecipitation. Genome-scale CRISPRa screen, overexpression and knockdown experiments, subcutaneous xenograft models, co-immunoprecipitation (MTX1-CISD1 interaction), autophagy flux assays International Journal of Biological Sciences Medium 34421355
2015 High-throughput AP-MS (BioPlex network) identified MTX1 protein-protein interactions in HEK293T cells, placing MTX1 within a network community consistent with its mitochondrial outer membrane function and import complex role. Affinity purification mass spectrometry (AP-MS) of 2,594 human proteins in HEK293T cells Cell Low 26186194
2022 OpenCell endogenous tagging project determined the subcellular localization of MTX1 by live-cell confocal imaging of endogenously tagged protein, confirming mitochondrial localization and enabling identification of proximity interactors consistent with outer membrane complex membership. CRISPR-based endogenous tagging, confocal live-cell imaging, affinity purification mass spectrometry Science Medium 35271311

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2000 Caco-2 versus Caco-2/HT29-MTX co-cultured cell lines: permeabilities via diffusion, inside- and outside-directed carrier-mediated transport. Journal of pharmaceutical sciences 276 10664539
2012 Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nature genetics 241 22797727
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
2004 Lineage-specific gene duplication and loss in human and great ape evolution. PLoS biology 224 15252450
2016 Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Molecular cell 220 27499296
2008 Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell culture model used to predict iron bioavailability. The Journal of nutritional biochemistry 204 18715773
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
1996 HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans. Journal of pharmaceutical sciences 199 8897273
2016 Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Annals of the rheumatic diseases 188 27993829
2007 The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11. FEBS letters 180 17624330
2014 A tunable Caco-2/HT29-MTX co-culture model mimicking variable permeabilities of the human intestine obtained by an original seeding procedure. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 163 24704198
2005 Dissection of the mitochondrial import and assembly pathway for human Tom40. The Journal of biological chemistry 163 15644312
2015 Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex. Biochimica et biophysica acta 160 26477565
2011 MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization. Molecular biology of the cell 150 22114354
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2020 Comparative Application of BioID and TurboID for Protein-Proximity Biotinylation. Cells 146 32344865
2011 Combined treatment of etanercept and MTX reverses Th1/Th2, Th17/Treg imbalance in patients with rheumatoid arthritis. Journal of clinical immunology 134 21562776
2017 Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mitophagy Pathway. Molecular cell 116 29149599
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
1997 Metaxin is a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion. The Journal of biological chemistry 111 9045676
2001 HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption: role of the mucus layer. Journal of pharmaceutical sciences 105 11745719
2019 Mitochondria-hubs for regulating cellular biochemistry: emerging concepts and networks. Open biology 99 31387448
2013 A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Annals of oncology : official journal of the European Society for Medical Oncology 96 23504948
2007 Conserved roles of Sam50 and metaxins in VDAC biogenesis. EMBO reports 95 17510655
2020 Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism. Nature metabolism 92 32694731
2010 Defining conditions for the co-culture of Caco-2 and HT29-MTX cells using Taguchi design. Journal of pharmacological and toxicological methods 91 20159047
1997 Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease. Genome research 88 9331372
2013 Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia. Pharmacogenetics and genomics 86 23222202
2015 Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center. British journal of haematology 75 26648336
2021 Caco-2/HT29-MTX co-cultured cells as a model for studying physiological properties and toxin-induced effects on intestinal cells. PloS one 64 34618824
2021 Cancer-associated fibroblast-derived exosomal microRNA-24-3p enhances colon cancer cell resistance to MTX by down-regulating CDX2/HEPH axis. Journal of cellular and molecular medicine 58 33621425
2006 Phase II study of MTX-HSA in combination with cisplatin as first line treatment in patients with advanced or metastatic transitional cell carcinoma. Investigational new drugs 55 16699974
2001 Methotrexate (MTX) inhibits osteoblastic differentiation in vitro: possible mechanism of MTX osteopathy. The Journal of rheumatology 55 11246658
2010 An open-label pilot study of the efficacy and safety of anakinra in patients with psoriatic arthritis refractory to or intolerant of methotrexate (MTX). Clinical rheumatology 52 20532937
2013 An immunological biomarker to predict MTX response in early RA. Annals of the rheumatic diseases 51 23989988
2017 Interaction of cruciferin-based nanoparticles with Caco-2 cells and Caco-2/HT29-MTX co-cultures. Acta biomaterialia 47 29030304
2008 Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX. Rheumatology (Oxford, England) 47 18539621
2004 Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX. Rheumatology (Oxford, England) 47 15199219
1994 Expression of cytochrome P-450 3A in HT29-MTX cells and Caco-2 clone TC7. FEBS letters 47 7988682
2018 CP-25 combined with MTX/ LEF ameliorates the progression of adjuvant-induced arthritis by the inhibition on GRK2 translocation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 46 30557832
2018 Toxicological impact of acute exposure to E171 food additive and TiO2 nanoparticles on a co-culture of Caco-2 and HT29-MTX intestinal cells. Mutation research. Genetic toxicology and environmental mutagenesis 46 31561898
2020 Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes. Theranostics 44 32929336
2014 Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus. Bone marrow transplantation 44 24566710
2012 Monocyte populations as markers of response to adalimumab plus MTX in rheumatoid arthritis. Arthritis research & therapy 44 22838733
1996 Structure and organization of the human metaxin gene (MTX) and pseudogene. Genomics 43 8660965
2017 Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy. Neurology 42 28747447
2018 Metabolism of Caprine Milk Carbohydrates by Probiotic Bacteria and Caco-2:HT29⁻MTX Epithelial Co-Cultures and Their Impact on Intestinal Barrier Integrity. Nutrients 39 30041482
1990 Cell cycle-dependent DHFR and t-PA production in cotransfected, MTX-amplified CHO cells revealed by dual-laser flow cytometry. Experimental cell research 38 2110526
2020 Small silica nanoparticles transiently modulate the intestinal permeability by actin cytoskeleton disruption in both Caco-2 and Caco-2/HT29-MTX models. Archives of toxicology 37 32162006
2006 Bacillus sphaericus mosquitocidal toxin (MTX) and pierisin: the enigmatic offspring from the family of ADP-ribosyltransferases. Molecular microbiology 37 17076664
2020 MTX-Loaded Dual Thermoresponsive and pH-Responsive Magnetic Hydrogel Nanocomposite Particles for Combined Controlled Drug Delivery and Hyperthermia Therapy of Cancer. Molecular pharmaceutics 34 33300343
1997 Effect of methotrexate (MTX) on NAD(P)+ dehydrogenases of HeLa cells: malic enzyme, 2-oxoglutarate and isocitrate dehydrogenases. Cell biochemistry and function 34 9415972
2023 Development of an Inflammation-Triggered In Vitro "Leaky Gut" Model Using Caco-2/HT29-MTX-E12 Combined with Macrophage-like THP-1 Cells or Primary Human-Derived Macrophages. International journal of molecular sciences 33 37108590
2018 Targeted hexagonal Pd nanosheet combination therapy for rheumatoid arthritis via the photothermal controlled release of MTX. Journal of materials chemistry. B 33 32254955
2013 Intestinal transport of methylmercury and inorganic mercury in various models of Caco-2 and HT29-MTX cells. Toxicology 32 23793072
2021 Efficacy and safety of prophylactic high-dose MTX in high-risk DLBCL: a treatment intent-based analysis. Blood advances 31 33881464
1995 Binding of muscarinic toxins MTx1 and MTx2 from the venom of the green mamba Dendroaspis angusticeps to cloned human muscarinic cholinoceptors. Toxicon : official journal of the International Society on Toxinology 31 7778123
2011 Adhesion of bile-adapted Bifidobacterium strains to the HT29-MTX cell line is modified after sequential gastrointestinal challenge simulated in vitro using human gastric and duodenal juices. Research in microbiology 30 21419219
2020 Co-culture model of Caco-2/HT29-MTX cells: A promising tool for investigation of phycotoxins toxicity on the intestinal barrier. Chemosphere 29 34756374
2019 Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients. Arthritis research & therapy 29 31242943
2016 Mucus interactions with liposomes encapsulating bioactives: Interfacial tensiometry and cellular uptake on Caco-2 and cocultures of Caco-2/HT29-MTX. Food research international (Ottawa, Ont.) 29 28290290
2010 Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines. Journal of biomedical materials research. Part A 29 19213059
1998 Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G-CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's lymphoma. Bone marrow transplantation 29 9613778
2015 Capability of exopolysaccharide-producing Lactobacillus paraplantarum BGCG11 and its non-producing isogenic strain NB1, to counteract the effect of enteropathogens upon the epithelial cell line HT29-MTX. Food research international (Ottawa, Ont.) 28 28411984
2016 Influence of ADORA2A gene polymorphism on leukoencephalopathy risk in MTX-treated pediatric patients affected by hematological malignancies. Pediatric blood & cancer 27 27399166
2011 Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD. Bone marrow transplantation 27 21423118
2021 Dexmedetomidine reverses MTX-induced neurotoxicity and inflammation in hippocampal HT22 cell lines via NCOA4-mediated ferritinophagy. Aging 26 33632938
2020 Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats. Naunyn-Schmiedeberg's archives of pharmacology 26 32103295
2017 pH- and thermo-sensitive MTX-loaded magnetic nanocomposites: synthesis, characterization, and in vitro studies on A549 lung cancer cell and MR imaging. Drug development and industrial pharmacy 26 29098882
2007 Mtx toxins synergize Bacillus sphaericus and Cry11Aa against susceptible and insecticide-resistant Culex quinquefasciatus larvae. Applied and environmental microbiology 26 17704274
2022 Role of Short Chain Fatty Acids to Counteract Inflammatory Stress and Mucus Production in Human Intestinal HT29-MTX-E12 Cells. Foods (Basel, Switzerland) 25 35804798
2014 Synthetic polyglutamylation of dual-functional MTX ligands for enhanced combined cytotoxicity of poly(I:C) nanoplexes. Molecular pharmaceutics 25 24754871
2016 Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway. European journal of drug metabolism and pharmacokinetics 24 26077125
2011 Adenosine abolishes MTX-induced suppression of osteoclastogenesis and inflammatory bone destruction in adjuvant-induced arthritis. Laboratory investigation; a journal of technical methods and pathology 24 21339747
2018 Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes. Rheumatology (Oxford, England) 23 29746672
2017 Oleic Acid Uptake Reveals the Rescued Enterocyte Phenotype of Colon Cancer Caco-2 by HT29-MTX Cells in Co-Culture Mode. International journal of molecular sciences 23 28726765
2011 The role of HLA--G 14-bp polymorphism in allo-HSCT after short-term course MTX for GvHD prophylaxis. Bone marrow transplantation 23 21399669
2022 D-mannose functionalized MgAl-LDH/Fe-MOF nanocomposite as a new intelligent nanoplatform for MTX and DOX co-drug delivery. International journal of pharmaceutics 22 35970281
2013 CD147 promotes MTX resistance by immune cells through up-regulating ABCG2 expression and function. Journal of dermatological science 22 23622764
2019 Systemic HD-MTX for CNS prophylaxis in high-risk DLBCL patients: a prospectively collected, single-center cohort analysis. International journal of hematology 21 31115880
2020 Repeated exposure of Caco-2 versus Caco-2/HT29-MTX intestinal cell models to (nano)silver in vitro: Comparison of two commercially available colloidal silver products. The Science of the total environment 20 33254900
2021 Association of MTHFR and ABCB1 polymorphisms with MTX-induced mucositis in Chinese paediatric patients with acute lymphoblastic leukaemia, lymphoma or osteosarcoma-A retrospective cohort study. Journal of clinical pharmacy and therapeutics 19 34346513
2015 Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response. Theranostics 19 26379787
2021 Characterization of increased mucus production of HT29-MTX-E12 cells grown under Semi-Wet interface with Mechanical Stimulation. PloS one 18 34928974
2020 Silencing DVL3 defeats MTX resistance and attenuates stemness via Notch Signaling Pathway in colorectal cancer. Pathology, research and practice 18 32414668
2019 Preparation and Characterization of Fe3O4@MTX Magnetic Nanoparticles for Thermochemotherapy of Primary Central Nervous System Lymphoma in vitro and in vivo. International journal of nanomedicine 18 31824157
2018 The impact of apical and basolateral albumin on intestinal zinc resorption in the Caco-2/HT-29-MTX co-culture model. Metallomics : integrated biometal science 18 29931006
2016 Screening of Cytotoxic B. cereus on Differentiated Caco-2 Cells and in Co-Culture with Mucus-Secreting (HT29-MTX) Cells. Toxins 18 27827957
2014 Novel DOX-MTX nanoparticles improve oral SCC clinical outcome by down regulation of lymph dissemination factor VEGF-C expression in vivo: oral and IV modalities. Asian Pacific journal of cancer prevention : APJCP 18 25124602
1983 Characterization of two paralysing protein toxins (A-MTX and B-MTX), isolated from a homogenate of the wasp Microbracon hebetor (Say). Comparative biochemistry and physiology. B, Comparative biochemistry 18 6884005
2006 The effect of methotrexate (MTX) on expression of signalling lymphocytic activation molecule (SLAM) in patients with rheumatoid arthritis (RA) and its role in the regulation of cytokine production. Scandinavian journal of rheumatology 17 16882589
2022 Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients. Cancer chemotherapy and pharmacology 16 35157101
2016 Ubiquitous Chromatin Opening Elements (UCOEs) effect on transgene position and expression stability in CHO cells following methotrexate (MTX) amplification. Biotechnology journal 16 26632501
2014 Impact analysis of autoantibody level and NR2 antibody level in neuropsychiatric SLE treated by methylprednisolone combined with MTX and DXM intrathecal injection. Cell biochemistry and biophysics 16 24845150
2009 Different responses of Fe transporters in Caco-2/HT29-MTX cocultures than in independent Caco-2 cell cultures. Cell biology international 16 19524686
2022 ADSC-Exosomes Alleviate MTX-induced Rat Neuronal Damage by Activating Nrf2-ARE Pathway. Journal of molecular neuroscience : MN 15 35322376
2016 Protective Role of Silymarin on Hepatic and Renal Toxicity Induced by MTX Based Chemotherapy in Children with Acute Lymphoblastic Leukemia. Mediterranean journal of hematology and infectious diseases 15 27648206
2014 Effect of edible oils on quercetin, kaempferol and galangin transport and conjugation in the intestinal Caco-2/HT29-MTX co-culture model. Food & function 15 24525490
2014 DOX-MTX-NPs augment p53 mRNA expression in OSCC model in rat: effects of IV and oral routes. Asian Pacific journal of cancer prevention : APJCP 15 25339032
2014 Synthesis and formulation of methotrexate (MTX) conjugated LaF3:Tb(3+)/chitosan nanoparticles for targeted drug delivery applications. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 25661354
2011 Homozygosity for the MTX1 c.184T>A (p.S63T) alteration modifies the age of onset in GBA-associated Parkinson's disease. Neurogenetics 15 21837367
1988 Impairment of methotrexate (MTX)-polyglutamate formation of MTX-resistant K562 cell lines. Japanese journal of cancer research : Gann 15 2465288
1985 Syntheses and evaluation as antifolates of MTX analogues derived from 2, omega-diaminoalkanoic acids. Journal of medicinal chemistry 15 4020824
2024 A First Metabolite Analysis of Norfolk Island Pine Resin and Its Hepatoprotective Potential to Alleviate Methotrexate (MTX)-Induced Hepatic Injury. Pharmaceuticals (Basel, Switzerland) 14 39065818
2023 MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer. International journal of molecular sciences 14 37108769
2022 Discovery of a Highly Specific Anti-methotrexate (MTX) DNA Aptamer for Antibody-Independent MTX Detection. Analytical chemistry 14 36449359
2019 MTHFR C677T polymorphism increases MTX sensitivity via the inhibition of S-adenosylmethionine and de novo purine synthesis. Clinical science (London, England : 1979) 14 30606816
2023 Is methotrexate safe for men with an immune-mediated inflammatory disease and an active desire to become a father? Results of a prospective cohort study (iFAME-MTX). Annals of the rheumatic diseases 13 37263756
2023 MTX-13, a Novel PTK7-Directed Antibody-Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors. Molecular cancer therapeutics 13 37352387
2023 Caco-2 Cell Sheet Partially Laminated with HT29-MTX Cells as a Novel In Vitro Model of Gut Epithelium Drug Permeability. Pharmaceutics 13 37765306
2021 Branching out the aerolysin, ETX/MTX-2 and Toxin_10 family of pore forming proteins. Journal of invertebrate pathology 13 33775676
2019 Adipocytes as lipid sensors of oleic acid transport through a functional Caco-2/HT29-MTX intestinal barrier. Adipocyte 13 30905315
1992 Monoclonal antibody targeting of methotrexate (MTX) against MTX-resistant tumour cell lines. British journal of cancer 13 1616855
2022 TNF-α Inhibitors in Combination with MTX Reduce Circulating Levels of Heparan Sulfate/Heparin and Endothelial Dysfunction Biomarkers (sVCAM-1, MCP-1, MMP-9 and ADMA) in Women with Rheumatoid Arthritis. Journal of clinical medicine 12 35887981
2021 Genome-scale CRISPRa screening identifies MTX1 as a contributor for sorafenib resistance in hepatocellular carcinoma by augmenting autophagy. International journal of biological sciences 12 34421355
2015 Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 12 26022160
2023 Histochemical, Immunohistochemical, and Biochemical Investigation of the Effect of Resveratrol on Testicular Damage Caused by Methotrexate (MTX). Reproductive sciences (Thousand Oaks, Calif.) 11 37268870
1999 ACNU, MTX and 5-FU penetration of rat brain tissue and tumors. Journal of neuro-oncology 11 10728905