Affinage

ADAM9

Disintegrin and metalloproteinase domain-containing protein 9 · UniProt Q13443

Length
819 aa
Mass
90.6 kDa
Annotated
2026-06-09
100 papers in source corpus 45 papers cited in narrative 45 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

ADAM9 is a membrane-anchored metalloprotease-disintegrin that controls cell-surface proteolysis and integrin-dependent adhesion across tissue remodeling, angiogenesis, and tumor progression (PMID:16230393, PMID:19273593). Its prodomain is removed by a furin-type convertase in the secretory pathway to yield a catalytically active enzyme that cleaves insulin B-chain, is sensitive to hydroxamate inhibitors but not to TIMP-1/-2/-4 (and only weakly to TIMP-3), distinguishing it biochemically from related ADAMs (PMID:9920899, PMID:12135759, PMID:28264989). As a sheddase it releases a broad substrate set including EGF and FGFR2 (PMID:16230393), EphB4, Tie-2, Flk-1, and VE-cadherin (PMID:19273593), collagen XVII (PMID:19574220), ACE (PMID:22480688), and ephrin-B1/B2 (PMID:35780836), and cleaves the latency-associated peptide of TGF-β1 to generate bioactive TGF-β1 that drives SMAD2/3 phosphorylation and Th17 differentiation (PMID:33911034). Independent of its catalytic activity, the disintegrin–cysteine-rich domain is a polyvalent ligand for multiple β1 integrins, modulating cell–matrix adhesion, ERK signaling and MMP induction, and migration (PMID:15361064, PMID:17704059, PMID:21135106), while ADAM9 association with β1 integrin governs integrin internalization and degradation to remodel focal adhesions (PMID:29142101). Shedding and adhesion functions are regulated through the cytoplasmic tail, which binds PKCδ to couple ectodomain shedding to signaling (PMID:9857183), and ADAM9 expression and activity are induced by reactive oxygen species (PMID:19273593). ADAM9 also acts indirectly by controlling ADAM10 membrane localization and thereby alpha-secretase activity (PMID:21956108), and serves as a proteinase-independent entry factor/cofactor for encephalomyocarditis virus (PMID:30723129, PMID:31409686). In cancer, ADAM9 stabilizes KRAS by preventing PAI-1/LC3-mediated selective autophagic degradation, and its small-molecule inhibition restricts PDAC progression (PMID:38267627). Loss-of-function mutation of ADAM9 causes cone-rod dystrophy/CORD9, with the primary lesion being failure of retinal pigment epithelium apical microvilli to invest photoreceptor outer segments (PMID:20806078).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 Medium

    Established that the ADAM9 cytoplasmic tail is a signaling adaptor by showing its proline-rich motifs bind the Src SH3 domain, framing the protein as more than a surface protease.

    Evidence Domain analysis, cell-surface biotinylation, and immunofluorescence of MDC9-expressing cells

    PMID:8647900

    Open questions at the time
    • Functional consequence of Src binding not demonstrated
    • No catalytic activity tested yet
  2. 1998 High

    Linked ADAM9 to regulated ectodomain shedding by showing PKCδ binds its cytoplasmic tail and that ADAM9 mediates proHB-EGF shedding, coupling intracellular signaling to surface proteolysis.

    Evidence Reciprocal Co-IP, dominant-negative/active PKCδ constructs, domain-deletion mutants, shedding assay

    PMID:9857183

    Open questions at the time
    • Physiological in vivo relevance not tested
    • Whether ADAM9 directly cleaves HB-EGF or acts via another sheddase unclear
  3. 1999 High

    Defined ADAM9 as a bona fide active metalloprotease processed by furin and regulated by cysteine-switch and phosphorylation, with a defined inhibitor sensitivity profile.

    Evidence Insulin B-chain cleavage, inhibitor profiling, cysteine-switch peptide assays, phosphorylation labeling

    PMID:9920899

    Open questions at the time
    • Physiological substrates not yet defined
    • In vivo activation state unknown
  4. 1999 Medium

    Expanded the cytoplasmic interactome to endophilin I, SH3PX1, and a MAD2-related protein, indicating precursor-selective trafficking/regulatory partnerships.

    Evidence Yeast two-hybrid screens with GST pulldown and Co-IP

    PMID:10527948 PMID:10531379

    Open questions at the time
    • Functional roles of endophilin/SH3PX1/MAD2β interactions not established
    • Precursor-selective binding mechanism unexplained
  5. 2002 High

    A genetic knockout showed ADAM9 is dispensable for HB-EGF shedding and APP processing in vivo, revealing functional redundancy and reframing earlier overexpression results.

    Evidence mdc9−/− mice with fibroblast shedding and neuronal Aβ/p3 assays

    PMID:11839819

    Open questions at the time
    • Redundant ADAMs not identified
    • Does not exclude context-specific roles
  6. 2005 High

    Defined the disintegrin–cysteine-rich domain as a polyvalent β1-integrin ligand controlling cell-matrix adhesion, separating an adhesion function from catalysis.

    Evidence GST-disintegrin pulldown, adhesion assays with integrin-blocking antibodies, GFP-chimera expression

    PMID:10752518 PMID:15361064

    Open questions at the time
    • Integrin selectivity rules not resolved
    • Signaling downstream of adhesion not yet mapped
  7. 2005 High

    Established ADAM9 substrates and tumor-promoting shedding (EGF, FGFR2, laminin) and showed secreted ADAM9 directly binds integrins to drive carcinoma invasion.

    Evidence W10 prostate cancer KO/overexpression mouse models, direct integrin-binding and laminin cleavage assays, protease-dead mutant

    PMID:15930291 PMID:16230393

    Open questions at the time
    • Relative contribution of soluble vs membrane ADAM9 in vivo unclear
    • Tumor-stage specificity not defined
  8. 2005 High

    Revealed that ADAM9 acts indirectly on alpha-secretase substrates by requiring and promoting ADAM10, establishing an epistatic relationship rather than direct redundancy.

    Evidence ADAM10−/− complementation, antisense knockdown, fluorimetric substrate assays

    PMID:16236709

    Open questions at the time
    • Mechanism of ADAM10 promotion not yet defined at this stage
    • Distinction from direct cleavage incomplete
  9. 2007 High

    Connected integrin engagement by the disintegrin–cysteine-rich domain to downstream ERK activation, MMP-9 induction, and motility, defining an outside-in signaling axis.

    Evidence Solid-phase binding, Co-IP, ERK phosphorylation, MMP-9 Western, keratinocyte migration assays

    PMID:17704059

    Open questions at the time
    • Whether signaling occurs in trans or cis unclear
    • In vivo relevance to keratinocyte biology untested here
  10. 2009 High

    Showed ADAM9 drives pathological neovascularization and identified ROS as an upstream inducer of ADAM9 expression and shedding of vascular substrates.

    Evidence Adam9−/− OIR/CNV/tumor models, overexpression shedding assays, H2O2 stimulation

    PMID:19273593

    Open questions at the time
    • Direct vs indirect cleavage of each vascular substrate not all confirmed
    • ROS-to-ADAM9 signaling mechanism not detailed
  11. 2009 High

    Defined ADAM9 as a major constitutive collagen XVII and ACE sheddase, tying its activity to keratinocyte basement-membrane biology and endothelial inflammation.

    Evidence Adam9−/− keratinocytes, ADAM10-selective inhibitor, LPS/HEK293 ACE shedding with catalytic mutant

    PMID:19574220 PMID:22480688

    Open questions at the time
    • Stimulus-specific regulation of collagen XVII shedding incomplete
    • ACE shedding study lower confidence on direct cleavage
  12. 2010 High

    Separated the opposing roles of the secreted and membrane isoforms in migration and linked ADAM9-driven adhesion to tumor-stroma interactions and metastasis.

    Evidence Isoform-specific and domain-mutant constructs, recombinant DC-9 adhesion assays, siRNA, wound-repair and migration models

    PMID:20376065 PMID:20736367 PMID:21135106

    Open questions at the time
    • Balance of isoform expression in tissues not quantified
    • How membrane ADAM9 suppresses migration mechanistically incomplete
  13. 2010 Medium

    Identified ADAM9 as the causative gene for cone-rod dystrophy/CORD9, establishing a Mendelian disease link and pointing to a role in RPE-photoreceptor microvillar interaction.

    Evidence Canine GWAS/sequencing of crd3, light/electron microscopy, electroretinography

    PMID:20806078

    Open questions at the time
    • Molecular function of ADAM9 in RPE microvilli undefined
    • Ortholog (canine) study; human mechanism inferred
  14. 2011 High

    Mechanistically resolved the ADAM9-ADAM10 relationship by showing the ADAM9 prodomain is a selective inhibitor and that ADAM9 controls ADAM10 membrane localization and alpha-secretase output.

    Evidence Recombinant prodomain Ki measurement, cell-based ADAM10 localization and sAPPα/β quantification

    PMID:21956108

    Open questions at the time
    • Whether ADAM9 sheds ADAM10 directly versus other mechanism unresolved
    • In vivo relevance to APP biology untested
  15. 2012 High

    Placed ADAM9 in a regulatory complex with MT1-MMP and FGFR2, where MT1-MMP inactivates ADAM9 to protect FGFR2 from shedding during skeletal development.

    Evidence Co-IP, Mmp14−/− and Adam9-depletion mice, genetic rescue, FGFR2 shedding and skeletal phenotyping

    PMID:22632802

    Open questions at the time
    • Structural basis of MT1-MMP cleavage of ADAM9 not defined
    • Generality beyond osteoblasts unknown
  16. 2015 High

    Defined ADAM9 as a stored neutrophil ECM-degrading protease and a direct platelet α6β1 ligand, linking it to acute lung injury and metastatic dissemination.

    Evidence Subcellular fractionation, in vitro ECM degradation, Adam9−/− lung-injury models, recombinant DC-9 platelet adhesion and α6β1 KO metastasis models

    PMID:25063875 PMID:25646025 PMID:27699237

    Open questions at the time
    • In vivo substrate spectrum during lung injury incompletely defined
    • Relative contribution of adhesion vs proteolysis to metastasis unresolved
  17. 2017 High

    Characterized constitutive EphB4 shedding and selective inhibitor profiles, and elaborated ADAM9-driven angiogenic and metastatic transcriptional programs in lung cancer.

    Evidence Cell-based shedding with E>A mutant, TIMP/small-molecule profiling, siRNA knockdown with microarray, tPA/CDCP1 cleavage, miR-1/miR-218 reporter assays, in vivo tumor models

    PMID:24705471 PMID:25060522 PMID:28264989 PMID:28537886 PMID:29118335

    Open questions at the time
    • Direct vs transcriptionally indirect effects on angiogenic factors not fully separated
    • miRNA-axis findings are Medium-confidence single-lab
  18. 2018 High

    Resolved a protease-independent role in integrin trafficking and linked ADAM9 to ROS-generating NOX1 in driving EMT, broadening its mechanism beyond shedding.

    Evidence siRNA, Co-IP with β1 integrin, internalization/recycling/degradation assays, NOX1 interaction and ROS measurement, EMT markers

    PMID:29142101 PMID:29432845

    Open questions at the time
    • Mechanism by which ADAM9 promotes integrin endocytosis undefined
    • NOX1 interaction is Medium-confidence single lab
  19. 2019 High

    Identified an entirely proteinase-independent function as an EMCV entry factor/cofactor mediating viral attachment and genome delivery.

    Evidence Genome-wide CRISPR and haploid screens, KO in multiple cell lines, RNA-transfection bypass, catalytic-dead reconstitution, neutralization and binding assays

    PMID:30723129 PMID:31409686

    Open questions at the time
    • Structural basis of EMCV-ADAM9 binding not resolved
    • Whether other picornaviruses use ADAM9 not addressed
  20. 2021 High

    Established ADAM9 as a TGF-β1 activator that cleaves LAP to drive Th17 differentiation, with ICER as a direct transcriptional activator, defining an immunological role in autoimmunity.

    Evidence Adam9−/− EAE model, T cell transfer, LAP cleavage, SMAD2/3 phosphorylation, ICER promoter binding, Th17 assays

    PMID:33911034

    Open questions at the time
    • Spatial control of latent TGF-β1 activation in vivo unclear
    • Other immune cell contributions not dissected
  21. 2022 Medium

    Demonstrated ephrin-B1/B2 cleavage and Akt/Wnt/mTOR modulation, with cross-species rescue of ADAM13 in neural crest induction, indicating conserved developmental signaling roles.

    Evidence ADAM9 KD in CRC lines, ephrin-B cleavage, Wnt/mTOR/Akt assays, Xenopus neural crest rescue

    PMID:35780836

    Open questions at the time
    • Cell-line-dependent signaling outcomes not mechanistically explained
    • Single lab
  22. 2024 High

    Revealed a non-shedding oncogenic mechanism whereby ADAM9 stabilizes KRAS by blocking PAI-1/LC3-mediated selective autophagy, and validated ADAM9 as a druggable PDAC target.

    Evidence Co-IP of KRAS-PAI-1-LC3, ADAM9 KO/inhibitor, autophagy/lysosomal degradation assays, spontaneous PDAC and PDX models

    PMID:38267627

    Open questions at the time
    • How ADAM9 physically prevents PAI-1-KRAS interaction undefined
    • Whether mechanism is shared across other RAS-driven tumors unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADAM9 integrates its distinct catalytic-dependent shedding, catalytic-independent integrin/adhesion, viral-cofactor, and protein-stabilization functions into a unified regulatory logic, and how isoform/localization balance is controlled in vivo, remains unresolved.
  • No structural model integrating disintegrin and protease functions
  • Mechanism switching between protease-dependent and -independent modes undefined
  • Regulation of secreted vs membrane isoform expression in tissues unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0098631 cell adhesion mediator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0016787 hydrolase activity 3 GO:0001618 virus receptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1474244 Extracellular matrix organization 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2
Partners
FGFR2ITGA6ITGB1MMP14NAA10NOX1PRKCDSRC
Complex memberships
ADAM9–Naa10p complexKRAS–PAI-1–LC3 autophagy complex (ADAM9-regulated)MT1-MMP–FGFR2–ADAM9 complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 MDC9 (ADAM9) cytoplasmic tail contains two proline-rich sequences that bind the SH3 domain of Src, demonstrating SH3 ligand function. MDC9 is present on the plasma membrane of NIH 3T3 fibroblasts as an ~84 kDa glycoprotein. Protein domain analysis, cell surface biotinylation, 125I-labeling, immunofluorescence of COS-7 cells expressing MDC9 The Journal of cell biology Medium 8647900
1998 PKCδ binds in vivo and in vitro to the cytoplasmic domain of MDC9/ADAM9. Constitutively active PKCδ or MDC9 overexpression induces ectodomain shedding of proHB-EGF, while MDC9 lacking the metalloprotease domain and kinase-negative PKCδ suppress TPA-induced HB-EGF ectodomain shedding. Co-immunoprecipitation (in vivo and in vitro binding), dominant-negative/constitutively active mutant overexpression, ectodomain shedding assay The EMBO journal High 9857183
1999 The prodomain of MDC9/ADAM9 is removed by a furin-type proprotein convertase in the secretory pathway before cell surface emergence. Soluble MDC9 metalloprotease domain is catalytically active, cleaving insulin B-chain. MDC9 activity is inhibited by hydroxamic acid metalloprotease inhibitors (low nM range). Cysteine-switch peptides inhibit MDC9 in low µM range, providing evidence for cysteine-switch regulation. MDC9 becomes phosphorylated upon phorbol ester (PMA) treatment. Biochemical cleavage assays (insulin B-chain), inhibitor profiling, cysteine-switch peptide inhibition, metabolic labeling/phosphorylation assay The Journal of biological chemistry High 9920899
1999 The cytoplasmic domains of MDC9/ADAM9 interact with two SH3 domain-containing proteins: endophilin I (SH3GL2/SH3p4) and a novel protein SH3PX1 (containing SH3 and PX domains). Both proteins preferentially bind the precursor but not the processed form of MDC9 in COS-7 cells. Yeast two-hybrid screen, GST pulldown with bacterial fusion proteins, co-immunoprecipitation from eukaryotic cells The Journal of biological chemistry High 10531379
1999 MDC9 co-expressed with APP695 in COS cells promotes exclusive alpha-secretory cleavage of APP upon phorbol ester treatment. Inhibition of MDC9 by the hydroxamate inhibitor SI-27 enhanced beta-secretase cleavage of APP. Co-expression in COS cells, APP cleavage assay (alpha-secretory site mutant), hydroxamate inhibitor treatment The Biochemical journal Medium 10510302
1999 The cytoplasmic domain of MDC9/ADAM9 interacts with a novel MAD2-related protein, MAD2β (23% identity to MAD2, a spindle assembly checkpoint component). Interaction confirmed biochemically. Yeast two-hybrid screen, biochemical confirmation of interaction The Biochemical journal Medium 10527948
2000 MDC9/ADAM9 is localized to the basolateral surface of renal cortical tubule cells and glomerular visceral epithelial cells, co-localizing with β1 integrin. Expression of soluble disintegrin domain in glomerular epithelial cells causes cell rounding and detachment, indicating functional role in epithelial cell-matrix adhesion. Immunohistochemistry, GFP-chimera expression, Western blot of kidney fractions, cell morphology assay Journal of the American Society of Nephrology Medium 10752518
2001 ADAM9 is involved in monocyte fusion (multinucleated giant cell formation). Anti-ADAM9 antibody blocks CD98-mediated and RANKL-mediated multinucleated giant cell formation. The metalloprotease inhibitor SI-27 (which suppresses ADAM9 activity) also suppresses this fusion. Antibody blocking assay, metalloprotease inhibitor treatment, RT-PCR for expression Cellular immunology Medium 11831872
2002 Loss of MDC9/ADAM9 (mdc9−/− mice) does not impair constitutive or stimulated HB-EGF ectodomain shedding in embryonic fibroblasts, nor does it alter APP alpha-secretase (p3) or beta/gamma-secretase (Aβ) processing in hippocampal neurons, arguing against essential non-redundant roles in these processes in vivo. Genetic knockout (mdc9−/− mice), ectodomain shedding assay in primary fibroblasts, Aβ/p3 measurement in hippocampal neurons Molecular and cellular biology High 11839819
2002 Soluble ADAM9 activity is not inhibited by TIMP-1, TIMP-2, TIMP-3, or TIMP-4 (tissue inhibitors of metalloproteinases), but can be inhibited by hydroxamate inhibitors, distinguishing it from ADAM10, ADAM12, ADAM17, and MT-MMPs. In vitro protease activity assay with TIMP inhibition profiling FEBS letters High 12135759
2002 A secreted splice variant of human ADAM9 (hADAM9s), lacking the C-terminal transmembrane and cytoplasmic domains, is secreted from transfected COS cells and has alpha-secretase-like activity for APP upon phorbol ester treatment. Cloning of splice variant, COS cell transfection, APP cleavage assay Biochemical and biophysical research communications Medium 12054541
2003 ADAM9, ADAM10, and ADAM17 each catalyze alpha-secretory cleavage of APP in COS-7 cells. Lipofection of dsRNA to suppress endogenous ADAM9 in A172 glioblastoma cells reduces alpha-secretase cleavage, indicating that endogenous ADAM9 contributes to constitutive and regulated alpha-secretase activity. Overexpression in COS-7 cells, RNAi knockdown in A172 cells, APP cleavage measurement Biochemical and biophysical research communications Medium 12535668
2005 A secreted form of ADAM9 (ADAM9-S) is secreted by hepatic stellate cells, binds directly to α6β4 and α2β1 integrins on colon carcinoma cells via its disintegrin domain, and promotes carcinoma invasion. ADAM9-S also cleaves laminin. Protease activity of ADAM9-S is required for invasion. Matrigel invasion assay, direct binding assay (disintegrin domain to integrins), laminin cleavage assay, protease-inactive mutant Cancer research High 15930291
2005 The disintegrin domain of ADAM9 is a polyvalent ligand for multiple β1 renal integrins (α1, α3, α6, αv, β1). Expression of ADAM9 on HEK-293 cells decreases adhesion to collagen I/IV, vitronectin, and laminin via competitive inhibition of cell-matrix binding through the disintegrin domain. The cysteine-rich domain alone has no effect on adhesion. Recombinant GST-disintegrin domain pulldown, adhesion assay with integrin-blocking antibodies, GFP-chimera expression, Western blot The Biochemical journal High 15361064
2005 ADAM9 participates in constitutive secretion of PrPc N1 fragment in HEK293 cells, TSM1 neurons, and fibroblasts; ADAM9 antisense reduces N1 and sAPPα recoveries. However, ADAM9 requires ADAM10 for this activity: ADAM9 cannot cleave alpha-secretase substrates in ADAM10−/− fibroblasts, but co-expression of ADAM9 and ADAM10 enhances activity beyond ADAM10 alone. ADAM9 contributes to PrPc processing indirectly by promoting shedding of ADAM10. Transient and stable transfection, antisense knockdown, ADAM10−/− fibroblasts, fluorimetric substrate assay, Western blot The Journal of biological chemistry High 16236709
2005 ADAM9 loss in the W10 prostate cancer mouse model results in mostly well-differentiated tumors, while ADAM9-expressing controls develop poorly differentiated tumors. ADAM9 overexpression in mouse prostate epithelium causes hyperplasia and prostatic intraepithelial neoplasia. In cell-based assays, ADAM9 cleaves and releases EGF and FGFR2iiib from cells. Genetic KO in tumor mouse model (W10 × mdc9−/−), prostate-specific overexpression transgenic mice, cell-based shedding assay Cancer research High 16230393
2007 The recombinant disintegrin-cysteine-rich domain of ADAM-9 specifically interacts with the β1 integrin subunit on keratinocytes (confirmed by solid-phase binding assay and co-immunoprecipitation). Engagement of integrin receptors by this domain induces ERK phosphorylation and increased MMP-9 synthesis. Keratinocytes adhering to immobilized ADAM-9 disintegrin-cysteine-rich domain show increased motility, partially dependent on MMP-9 induction. Solid-phase binding assay, antibody inhibition, Co-immunoprecipitation, ERK phosphorylation assay, MMP-9 Western blot, migration assay The Journal of biological chemistry High 17704059
2009 ADAM9 deficiency (Adam9−/−) significantly reduces pathological neovascularization in OIR (oxygen-induced retinopathy) and laser-induced choroidal neovascularization models, and reduces tumor growth from heterotopically injected melanoma cells. ADAM9 overexpression enhances shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin. ADAM9 expression and shedding are upregulated by reactive oxygen species (H2O2). Adam9−/− mouse models (OIR, CNV, tumor xenograft), cell-based overexpression shedding assay, ROS stimulation assay Molecular and cellular biology High 19273593
2009 ADAMs 9 and 10 are the major collagen XVII sheddases in primary keratinocytes. Adam9−/− keratinocytes show a 55% decrease in constitutive collagen XVII ectodomain shedding. H2O2 enhances ADAM9 expression and stimulates collagen XVII shedding in wild-type but not Adam9−/− skin/keratinocytes. Adam9−/− and Adam10−/− primary keratinocyte cultures, ADAM10-selective inhibitor (GI254023X), phorbol ester treatment, H2O2 stimulation, collagen XVII shedding assay The Journal of biological chemistry High 19574220
2009 LPS activates ADAM9-dependent shedding of ACE from endothelial cells. ADAM9 requires both membrane anchorage and its catalytic domain to shed ACE, as shown by transient transfection of ADAM9 and ACE cDNAs in HEK293 cells. siRNA knockdown, inhibitor profiling (TIMP-based), HEK293 co-transfection with ADAM9 and ACE, catalytic domain mutant Biochemical and biophysical research communications Medium 22480688
2010 ADAM9 expression in melanoma cells is required for adhesion to fibroblasts. The disintegrin-like and cysteine-rich domains of ADAM-9 mediate Mn2+-dependent integrin-mediated adhesion of melanoma cells and fibroblasts (via multiple β1 integrins, independent of RGD and ECD motifs). Interaction with soluble DC-9 induces MMP-1 and MMP-2 expression in fibroblasts and melanoma cells. ADAM9 silencing in fibroblasts abolishes cellular interactions and melanoma invasion. Recombinant DC-9 domain adhesion assay, integrin-blocking antibodies, siRNA knockdown, MMP expression assay, invasion assay The Journal of biological chemistry High 21135106
2010 Adam9−/− mice show accelerated wound repair due to increased keratinocyte migration. Re-epithelialization is faster in Adam9−/− wounds, and increased migration (not proliferation) of keratinocytes is responsible. This is mechanistically linked to modulation of collagen XVII shedding by ADAM9. Adam9−/− genetic KO, excisional wound model, immunolocalization, keratinocyte migration assay, proliferation assay The Journal of investigative dermatology High 20376065
2010 Secreted ADAM9 (ADAM9-S) promotes breast cancer cell migration via its metalloproteinase activity. Membrane-bound ADAM9 (ADAM9-L) suppresses migration independent of metalloproteinase activity but requiring a functional disintegrin domain and integrin binding. The two isoforms thus have opposing effects on migration. Isoform-specific overexpression, metalloproteinase-dead mutant, disintegrin domain mutant, migration assay Cancer research High 20736367
2010 An ADAM9 deletion (removing exons 15 and 16, introducing a premature stop and removing critical domains) causes cone-rod dystrophy 3 (crd3) in Glen of Imaal Terriers, establishing homology to human CORD9. Light and electron microscopy show the primary lesion is failure of retinal pigment epithelium apical microvilli to invest photoreceptor outer segments. Genome-wide association, sequencing, light and electron microscopy, electroretinography Molecular vision Medium 20806078
2011 The ADAM9 prodomain (proA9) is a competitive inhibitor of ADAM9 catalytic/disintegrin domain (Ki = 280 ± 34 nM) with high specificity. Inhibition of ADAM9 by proA9 in SY5Y neuroblastoma cells reduces ADAM10 shedding into the medium while increasing membrane-bound ADAM10, resulting in higher sAPPα and lower sAPPβ levels. This demonstrates that ADAM9 controls ADAM10 membrane localization and alpha-secretase activity. Recombinant prodomain expression from E. coli, competitive inhibition assay, Western blot, fluorescent peptide substrate assay (proteolytic activity matrix analysis), proteomic quantification The Journal of biological chemistry High 21956108
2012 MT1-MMP (MMP14) forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, protecting FGFR2 from ADAM9-mediated ectodomain shedding. In Mmp14−/− osteoblasts, ADAM9 is upregulated and FGFR2 shedding increases, compromising FGF-induced proliferation and signaling. Adam9 depletion completely rescues defective FGFR2 signaling and largely restores calvarial bone growth in Mmp14−/− embryos. Co-immunoprecipitation (complex formation), Mmp14−/− and Adam9 depletion mouse models, FGFR2 shedding assay, downstream signaling assay, skeletal phenotype analysis Developmental cell High 22632802
2014 ADAM9 enhances tissue plasminogen activator (tPA)-mediated cleavage and activation of the promigratory protein CDCP1, promoting lung cancer metastasis to the brain. Blocking this mechanism prolongs survival in tumor-bearing mice, and cooperates with dexamethasone and dasatinib treatment. In vivo tumor metastasis model, survival analysis, inhibitor combination studies, protein cleavage assay Cancer research Medium 25060522
2014 ADAM9 is stored in gelatinase and specific granules and secretory vesicles of human PMNs (not synthesized de novo). PMN activation with degranulating agonists rapidly increases surface ADAM9. ADAM9 degrades ECM proteins (fibronectin, entactin, laminin, insoluble elastin) as potently as MMP-9, but does not degrade type I, III, or IV collagens or denatured collagens in vitro. Adam9 increases mortality and promotes alveolar-capillary barrier injury during LPS- and bleomycin-induced acute lung injury in mice; Adam9 does not regulate PMN/macrophage recruitment. Subcellular fractionation, flow cytometry, in vitro ECM degradation assays, Adam9−/− mouse lung injury models Journal of immunology High 25063875
2015 Platelet integrin α6β1 directly binds to ADAM9 on tumor cell surfaces via the disintegrin-cysteine domain of ADAM9 (DC-9 recombinant protein). This platelet-tumor cell interaction promotes platelet activation, tumor cell extravasation, and efficient lung metastasis. Genetic deficiency of integrin α6β1 on platelets markedly decreases experimental and spontaneous lung metastasis. Knockdown approach (siRNA), static and flow-based adhesion assays with recombinant DC-9, α6β1 KO mouse model (experimental and spontaneous metastasis), pharmacological inhibition JCI insight High 27699237
2015 TNC (tenascin-C) stimulates BTIC (brain tumor-initiating cell) invasiveness in a metalloproteinase-dependent manner involving ADAM-9. TNC increases ADAM-9 protein expression in 4 BTIC lines. RNAi-mediated ADAM-9 knockdown and inhibition of JNK attenuate TNC-stimulated ADAM-9 expression, proteolytic activity, and BTIC invasiveness. Microarray gene expression screen, lentiviral RNAi knockdown, ADAM-9 activity assay, JNK inhibitor treatment, orthotopic xenograft Neuro-oncology Medium 25646025
2017 ADAM9 constitutively sheds EphB4 in a manner not stimulated by phorbol esters, pervanadate, or calcium ionophores. ADAM9 is inhibited by TIMP-3 (10 nM) but not by TIMP-1 or TIMP-2 (up to 20 nM). Novel non-hydroxamate small-molecule inhibitors selectively inhibit ADAM9-dependent proteolysis over ADAM10 or ADAM17. Cell-based shedding assay with catalytically inactive ADAM9 E>A mutant as control, TIMP inhibitor profiling, small-molecule library screen The Biochemical journal High 28264989
2017 ADAM9 promotes lung cancer progression through vascular remodeling by upregulating VEGFA, ANGPT2, and PLAT (tPA). Silencing ADAM9 in lung cancer cells decreases expression of these angiogenic factors, reduces angiogenesis and vascular remodeling, and inhibits tumor growth in vivo. ADAM9 siRNA knockdown, microarray, in vivo tumor model, angiogenesis assay Scientific reports Medium 29118335
2017 ADAM9 knockdown reduces EGFR signaling and increases miR-1 expression in lung cancer cells. miR-1 directly targets the 3'UTR of CDCP1, inhibiting its translation. Thus ADAM9 down-regulates miR-1 via EGFR signaling, which in turn enhances CDCP1 expression to promote lung cancer progression. Luciferase reporter assay, EGFR signaling analysis, miR-1 expression measurement, tumor metastasis mouse model, miR-1 overexpression Oncotarget Medium 28537886
2017 ADAM9 upregulates N-cadherin (CDH2) expression in aggressive lung adenocarcinoma cells by suppressing miR-218. miR-218 is generated from pri-miR-218-1 located in SLIT2. ADAM9 knockdown upregulates SLIT2 and miR-218, which then down-regulates CDH2. miRNA microarray, luciferase assay, Western blot, siRNA knockdown of ADAM9 PloS one Medium 24705471
2018 IL-6 upregulates ADAM9 expression in HCC cells via the JNK signaling pathway. ADAM9 promotes HCC cell invasion and EMT by interacting with NADPH oxidase 1 (NOX1) and inducing reactive oxygen species (ROS) generation. ADAM9 knockdown inhibits IL-6-induced EMT. JNK inhibitor treatment, siRNA knockdown, NOX1 interaction assay, ROS measurement, migration/invasion assay, EMT marker Western blot Cancer letters Medium 29432845
2018 ADAM9 loss (siRNA knockdown) increases β1 integrin levels independently of protease activity. ADAM9 co-immunoprecipitates with β1 integrin. In ADAM9-silenced cells, β1 integrin internalization and degradation are significantly decreased (with no effect on recycling), altering focal adhesion formation, actin stress fibers, cell adhesion and migration. siRNA knockdown, co-immunoprecipitation, β1 integrin internalization/recycling/degradation assays, focal adhesion staining, migration assay Journal of cell science High 29142101
2019 ADAM9 is required for the early stages (entry/genome delivery) of EMCV (encephalomyocarditis virus) infection. CRISPR-mediated deletion of ADAM9 renders cells highly resistant to EMCV. Bypassing entry by delivering viral RNA directly to the cytosol restores EMCV replication in ADAM9 KO cells, indicating ADAM9 is not required for post-entry replication. Reconstitution of catalytically inactive ADAM9 in KO cells restores susceptibility, indicating a proteinase-independent role. Genome-wide CRISPR-Cas9 KO screen, ADAM9 CRISPR deletion in multiple cell lines, viral RNA transfection bypass experiment, reconstitution with inactive ADAM9 mutant mBio High 30723129
2019 ADAM9 facilitates attachment of EMCV to the cell surface, functioning as a receptor or cofactor for EMCV entry independent of its metalloproteinase activity (pharmacological metalloproteinase inhibition did not affect infection; catalytically inactive ADAM9 restored susceptibility in KO cells). Haploid genetic screen, CRISPR KO cell lines, neutralization assays with ADAM9-specific antiserum, soluble receptor proteins, cell-surface binding assays, catalytically inactive ADAM9 reconstitution mBio High 31409686
2019 ADAM9 contributes to vascular invasion in PDAC by mediating cell migration and adhesion to fibronectin, tenascin, and vitronectin (dependent on its catalytic activity). ADAM9 facilitates anchorage-independent growth. ADAM9 promotes angiogenesis in vitro and in vivo and regulates the levels of angiogenic factors including shed HB-EGF. ADAM9 post-translationally regulates integrin abundance in AsPC1 cells. siRNA gene silencing, migration and adhesion assays, anchorage-independent growth assay, HUVEC sprout formation with conditioned medium, orthotopic mouse model, immunoblotting Molecular oncology Medium 30556643
2020 Naa10p (N-α-acetyltransferase 10 protein) forms a complex with ADAM9 to maintain ADAM9 protein stability, promoting AIPC (androgen-independent prostate cancer) invasive ability independently of Naa10p acetyltransferase activity. ADAM9 also exerts positive feedback regulation on Naa10p. Co-immunoprecipitation, siRNA knockdown, overexpression, in vitro/in vivo invasion assays, xenograft Cell death & disease Medium 32719332
2021 ADAM9 cleaves the latency-associated peptide (LAP) of TGF-β1 to produce bioactive TGF-β1, which promotes SMAD2/3 phosphorylation and Th17 cell differentiation. Inducible cAMP early repressor (ICER) binds directly to the ADAM9 promoter and promotes its transcription. Adam9-deficient mice show mitigated experimental autoimmune encephalomyelitis (EAE). Adam9−/− mouse EAE model, T cell transfer assay, TGF-β1/LAP cleavage assay, SMAD2/3 phosphorylation assay, ICER promoter-binding (ChIP implied), Th17 differentiation assay Proceedings of the National Academy of Sciences of the United States of America High 33911034
2021 USP39 promotes glioma cell migration and invasion by facilitating ADAM9 mRNA maturation (splicing), increasing ADAM9 expression. Overexpression of ADAM9 rescues the reduced migration/invasion caused by USP39 depletion. shRNA knockdown, gene expression profiling, mRNA maturation assay, rescue by ADAM9 overexpression, in vivo invasion model Molecular oncology Medium 33811456
2022 ADAM9 cleaves ephrin-B1 and ephrin-B2 in mammalian (colorectal cancer) cells, can substitute for Xenopus ADAM13 in neural crest induction, and its knockdown reduces Akt kinase activity. ADAM9 KD differentially regulates Wnt and mTOR signaling downstream of Akt in a cell-line-dependent manner. ADAM9 KD in CRC cell lines, luciferase-based Wnt reporter, mTOR pathway assay, Akt kinase assay, Xenopus neural crest induction rescue experiment The Journal of biological chemistry Medium 35780836
2022 The secreted isoform of ADAM9 (ADAM9s) from cancer-associated fibroblasts (CAFs) with Immature desmoplastic reaction promotes CRC cell proliferation and migration. Knockdown of ADAM9s in these CAFs abrogates their tumor-promoting effects. CAF isolation from patient tissue, conditioned media assay, ADAM9s knockdown, CRC cell proliferation/migration assays, subcutaneous and orthotopic mouse models International journal of cancer Medium 35080810
2024 ADAM9 stabilizes wild-type and mutant KRAS proteins in PDAC. ADAM9 loss increases interaction of KRAS with PAI-1 (plasminogen activator inhibitor 1), which functions as a selective autophagy receptor together with LC3, triggering lysosomal degradation of KRAS. A small-molecule ADAM9 inhibitor restricts PDAC disease progression in spontaneous models, and combination with gemcitabine elicits regression of patient-derived tumors. Co-immunoprecipitation (KRAS-PAI-1-LC3 complex), ADAM9 KO/inhibitor experiments, autophagy/lysosomal degradation assays, spontaneous PDAC mouse model, PDX model Nature cancer High 38267627

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. The EMBO journal 458 9857183
1999 Metalloprotease-disintegrin MDC9: intracellular maturation and catalytic activity. The Journal of biological chemistry 269 9920899
2003 Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase. Biochemical and biophysical research communications 233 12535668
1999 Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein. The Biochemical journal 216 10510302
1996 MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains. The Journal of cell biology 180 8647900
2002 Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life. Molecular and cellular biology 169 11839819
2005 A secreted form of ADAM9 promotes carcinoma invasion through tumor-stromal interactions. Cancer research 153 15930291
1999 Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. The Journal of biological chemistry 149 10531379
2005 The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer. International journal of oncology 147 15586220
2011 MiR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9. Molecular cancer research : MCR 130 22064652
2003 Expression of ADAM-9 mRNA and protein in human breast cancer. International journal of cancer 124 12767059
2002 The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs. FEBS letters 121 12135759
2004 Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis. Cancer research 117 15205330
2005 The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. The Journal of biological chemistry 113 16236709
2016 Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell-derived ADAM9. JCI insight 108 27699237
2014 DNMT1-microRNA126 epigenetic circuit contributes to esophageal squamous cell carcinoma growth via ADAM9-EGFR-AKT signaling. Clinical cancer research : an official journal of the American Association for Cancer Research 99 25512445
2005 Critical function for ADAM9 in mouse prostate cancer. Cancer research 97 16230393
2017 Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways. Biochimica et biophysica acta. Molecular cell research 94 28648644
2020 An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases. International journal of molecular sciences 87 33096780
2009 ADAM9 is involved in pathological retinal neovascularization. Molecular and cellular biology 80 19273593
2002 A secreted form of human ADAM9 has an alpha-secretase activity for APP. Biochemical and biophysical research communications 80 12054541
2009 Shedding of collagen XVII/BP180 in skin depends on both ADAM10 and ADAM9. The Journal of biological chemistry 78 19574220
2014 ADAM9 promotes lung cancer metastases to brain by a plasminogen activator-based pathway. Cancer research 76 25060522
2019 miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A. Journal of experimental & clinical cancer research : CR 70 31227006
2012 MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis. Developmental cell 70 22632802
2014 MicroRNA-126 inhibits invasion in bladder cancer via regulation of ADAM9. British journal of cancer 69 24823697
2009 ADAM-9, ADAM-15, and ADAM-17 are upregulated in macrophages in advanced human atherosclerotic plaques in aorta and carotid and femoral arteries--Tampere vascular study. Annals of medicine 69 19253070
1999 Evidence for an interaction of the metalloprotease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2), and of the metalloprotease-disintegrin MDC9 with a novel MAD2-related protein, MAD2beta. The Biochemical journal 69 10527948
2008 ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression. BMC cancer 67 18582378
2015 MiR-126 regulated breast cancer cell invasion by targeting ADAM9. International journal of clinical and experimental pathology 65 26261534
2015 MiR-33a suppresses breast cancer cell proliferation and metastasis by targeting ADAM9 and ROS1. Protein & cell 62 26507842
2020 Circ-ADAM9 targeting PTEN and ATG7 promotes autophagy and apoptosis of diabetic endothelial progenitor cells by sponging mir-20a-5p. Cell death & disease 58 32661238
2011 ADAM9 inhibition increases membrane activity of ADAM10 and controls α-secretase processing of amyloid precursor protein. The Journal of biological chemistry 58 21956108
2019 Circular RNA circ_0020123 promotes non-small cell lung cancer progression by acting as a ceRNA for miR-488-3p to regulate ADAM9 expression. Biochemical and biophysical research communications 57 31153639
2003 Increased expression of disintegrin-metalloproteinases ADAM-15 and ADAM-9 following upregulation of integrins alpha5beta1 and alphavbeta3 in atherosclerosis. Journal of cellular biochemistry 56 12858346
2018 The pleiotropic roles of ADAM9 in the biology of solid tumors. Cellular and molecular life sciences : CMLS 55 29550974
2014 ADAM9 is a novel product of polymorphonuclear neutrophils: regulation of expression and contributions to extracellular matrix protein degradation during acute lung injury. Journal of immunology (Baltimore, Md. : 1950) 55 25063875
2017 miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting ADAM9 and TGFBR2. Cancer research 54 28209612
2010 Secreted and membrane-bound isoforms of protease ADAM9 have opposing effects on breast cancer cell migration. Cancer research 52 20736367
2010 The disintegrin-like and cysteine-rich domains of ADAM-9 mediate interactions between melanoma cells and fibroblasts. The Journal of biological chemistry 51 21135106
2001 Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes. Cellular immunology 51 11831872
2019 Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression. Artificial cells, nanomedicine, and biotechnology 50 31810373
2015 ADAM-9 is a novel mediator of tenascin-C-stimulated invasiveness of brain tumor-initiating cells. Neuro-oncology 50 25646025
2007 Role of ADAM-9 disintegrin-cysteine-rich domains in human keratinocyte migration. The Journal of biological chemistry 49 17704059
2016 miR-203 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting oncogene ADAM9 and oncogenic long non-coding RNA HULC. Anti-cancer agents in medicinal chemistry 48 26179263
2007 Reactive oxygen species mediate androgen receptor- and serum starvation-elicited downstream signaling of ADAM9 expression in human prostate cancer cells. The Prostate 48 17342749
2017 ADAM9 promotes lung cancer progression through vascular remodeling by VEGFA, ANGPT2, and PLAT. Scientific reports 47 29118335
2018 ADAM9 mediates the interleukin-6-induced Epithelial-Mesenchymal transition and metastasis through ROS production in hepatoma cells. Cancer letters 46 29432845
2005 The disintegrin domain of ADAM9: a ligand for multiple beta1 renal integrins. The Biochemical journal 46 15361064
2014 Fisetin suppresses ADAM9 expression and inhibits invasion of glioma cancer cells through increased phosphorylation of ERK1/2. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 45 25527158
2005 Adam-9 expression and regulation in human skin melanoma and melanoma cell lines. International journal of cancer 45 15856464
2018 MicroRNA-126 inhibits proliferation and metastasis in prostate cancer via regulation of ADAM9. Oncology letters 44 29805636
2011 Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy. The Prostate 44 20672324
2009 ADAM9 as a potential target molecule in cancer. Current pharmaceutical design 43 19601830
2010 Accelerated wound repair in ADAM-9 knockout animals. The Journal of investigative dermatology 42 20376065
2010 An ADAM9 mutation in canine cone-rod dystrophy 3 establishes homology with human cone-rod dystrophy 9. Molecular vision 42 20806078
2014 The effect of disintegrin-metalloproteinase ADAM9 in gastric cancer progression. Molecular cancer therapeutics 41 25344581
2019 ADAM9 contributes to vascular invasion in pancreatic ductal adenocarcinoma. Molecular oncology 39 30556643
2019 Histone methyltransferase NSD2 mediates the survival and invasion of triple-negative breast cancer cells via stimulating ADAM9-EGFR-AKT signaling. Acta pharmacologica Sinica 37 30670815
2020 Role of ADAM9 and miR-126 in the development of abdominal aortic aneurysm. Atherosclerosis 36 32078829
1998 Blastocyst-dependent upregulation of metalloproteinase/disintegrin MDC9 expression in rabbit endometrium. Cell and tissue research 35 9716739
2019 Fisetin Suppresses the Proliferation and Metastasis of Renal Cell Carcinoma through Upregulation of MEK/ERK-Targeting CTSS and ADAM9. Cells 33 31438640
2018 MiR-129-5p functions as a tumor suppressor in gastric cancer progression through targeting ADAM9. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 33 29879625
2017 MiR-488 suppresses cell proliferation and invasion by targeting ADAM9 and lncRNA HULC in hepatocellular carcinoma. American journal of cancer research 33 29119055
2014 ADAM9 up-regulates N-cadherin via miR-218 suppression in lung adenocarcinoma cells. PloS one 33 24705471
2020 A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy. Cancers 31 32245188
2017 ADAM9 enhances CDCP1 by inhibiting miR-1 through EGFR signaling activation in lung cancer metastasis. Oncotarget 31 28537886
2014 miR-126 inhibits cell growth, invasion, and migration of osteosarcoma cells by downregulating ADAM-9. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 25213697
2009 Inhibition of platelets and tumor cell adhesion by the disintegrin domain of human ADAM9 to collagen I under dynamic flow conditions. Biochimie 31 19505527
2019 A Disintegrin and Metalloproteinase 9 Domain (ADAM9) Is a Major Susceptibility Factor in the Early Stages of Encephalomyocarditis Virus Infection. mBio 30 30723129
2012 LPS activates ADAM9 dependent shedding of ACE from endothelial cells. Biochemical and biophysical research communications 29 22480688
2016 MicroRNA-140 represses glioma growth and metastasis by directly targeting ADAM9. Oncology reports 28 27498787
2013 Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9. PloS one 28 23405089
2020 Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer. Cell death & disease 27 32719332
2016 microRNA-590 suppresses the tumorigenesis and invasiveness of non-small cell lung cancer cells by targeting ADAM9. Molecular and cellular biochemistry 27 27770372
2021 Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation. Molecular oncology 26 33811456
2009 Expression of ADAM9 in CIN3 lesions and squamous cell carcinomas of the cervix. Gynecologic oncology 26 19473694
2021 ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1. Proceedings of the National Academy of Sciences of the United States of America 25 33911034
2020 ADAM9 Mediates Triple-Negative Breast Cancer Progression via AKT/NF-κB Pathway. Frontiers in medicine 25 32637415
2013 ADAM9 silencing inhibits breast tumor cell invasion in vitro. Biochimie 25 23499592
2001 CORD9 a new locus for arCRD: mapping to 8p11, estimation of frequency, evaluation of a candidate gene. Investigative ophthalmology & visual science 25 11581183
2022 Preclinical Evaluation of IMGC936, a Next-Generation Maytansinoid-based Antibody-drug Conjugate Targeting ADAM9-expressing Tumors. Molecular cancer therapeutics 24 35511740
2017 ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126. Oncology reports 24 28260063
2024 Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy. Nature cancer 23 38267627
2018 Loss of ADAM9 expression impairs β1 integrin endocytosis, focal adhesion formation and cancer cell migration. Journal of cell science 23 29142101
2022 Cancer-associated fibroblasts at the unfavorable desmoplastic stroma promote colorectal cancer aggressiveness: Potential role of ADAM9. International journal of cancer 22 35080810
2012 Substance P activates ADAM9 mRNA expression and induces α-secretase-mediated amyloid precursor protein cleavage. Neuropharmacology 22 22244942
2000 Identification, cellular distribution and potential function of the metalloprotease-disintegrin MDC9 in the kidney. Journal of the American Society of Nephrology : JASN 22 10752518
2021 mir-126-5p Promotes Cisplatin Sensitivity of Non-Small-Cell Lung Cancer by Inhibiting ADAM9. BioMed research international 21 34055989
2013 Overexpression of ADAM9 Promotes Colon Cancer Cells Invasion. Journal of investigative surgery : the official journal of the Academy of Surgical Research 21 26981956
2019 Identification of the Cell-Surface Protease ADAM9 as an Entry Factor for Encephalomyocarditis Virus. mBio 20 31409686
2010 RNAi-mediated ADAM9 gene silencing inhibits metastasis of adenoid cystic carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 20422344
2022 The ADAM9/UBN2/AKR1C3 axis promotes resistance to androgen-deprivation in prostate cancer. American journal of cancer research 19 35141012
2022 Metalloprotease ADAM9 cleaves ephrin-B ligands and differentially regulates Wnt and mTOR signaling downstream of Akt kinase in colorectal cancer cells. The Journal of biological chemistry 19 35780836
2021 Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis. OncoTargets and therapy 19 33907420
2017 Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays. The Biochemical journal 19 28264989
2017 MicroRNA-154/ADAM9 axis inhibits the proliferation, migration and invasion of breast cancer cells. Oncology letters 19 29163713
2018 ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death. Cancer science 18 29247567
2017 Galangin increases ERK1/2 phosphorylation to decrease ADAM9 expression and prevents invasion in A172 glioma cells. Molecular medicine reports 18 29115634
2015 ADAM9 disintegrin domain activates human neutrophils through an autocrine circuit involving integrins and CXCR2. Journal of leukocyte biology 18 25765677

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