Affinage

VCAN

Versican core protein · UniProt P13611

Length
3396 aa
Mass
372.8 kDa
Annotated
2026-06-11
100 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VCAN (versican/PG-M/CSPG2) is a large modular chondroitin sulfate proteoglycan that organizes the extracellular matrix and transduces matrix signals controlling cell adhesion, migration, condensation, and morphogenesis (PMID:3759975, PMID:8314802). Its N-terminal G1 domain binds hyaluronan and link protein to assemble proteoglycan aggregates, with the B-B' subdomain sufficient for both interactions and the A subdomain enhancing hyaluronan binding and required for stable aggregate formation (PMID:12888576, PMID:16648631); this hyaluronan-organizing function is essential for ECM assembly, and its loss releases free HA fragments that engage CD44, elevate ERK1/2 phosphorylation, and trigger premature senescence (PMID:19164294). The C-terminal G3 domain provides calcium-dependent C-type lectin and heparin-binding activities dependent on the CRP-like module, mediates intermolecular disulfide bonding, and engages fibronectin, VEGF, non-RGD β1-integrin, and PSGL-1 to activate FAK, support adhesion, confer apoptosis resistance, promote angiogenesis, and bridge leukocytes (PMID:7961677, PMID:12846582, PMID:11805102, PMID:14766798, PMID:15522894). The core protein is expressed as alternatively spliced isoforms V0–V3 differing in CS-α and CS-β attachment domain content (PMID:8314802, PMID:7730339, PMID:7876137), and the CS-rich V0/V1 isoforms are required for mesenchymal condensation and chondrogenesis, neural crest haptotaxis, endocardial cushion formation, and ventricular septal morphogenesis (PMID:16257955, PMID:10851128, PMID:9758703, PMID:22692047). Intronic VCAN mutations that shift splicing toward V2/V3 and one mutation that abolishes an MMP cleavage site in the GAGβ domain cause Wagner vitreoretinopathy through isoform imbalance and altered vitreous ECM rather than simple loss of function (PMID:16877430, PMID:22739342, PMID:30657523). In disease, VCAN acts as a downstream effector of oncogenic and fibrotic programs—the Snail/PAPSS2 sulfation axis, TGF-β1/FAP, ERK5, and STAT5—and ADAMTS1 proteolysis of V1 generates fragments that transactivate EGFR to drive anoikis resistance and invasion (PMID:29955124, PMID:41800245, PMID:40617369, PMID:39333870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1986 High

    Established versican as a large embryonic CS proteoglycan that physically links hyaluronate to fibronectin and collagen, defining its core role as an ECM-organizing molecule whose distribution tracks mesenchymal condensation.

    Evidence Immunoprecipitation, affinity purification, and binding assays with multiple ECM ligands; metabolic labeling and immunofluorescence in chick limb bud

    PMID:3759975 PMID:3759976

    Open questions at the time
    • Causal role in condensation inferred from localization, not loss-of-function
    • Domain responsible for each ligand interaction not yet mapped
  2. 1993 High

    cDNA cloning resolved the modular domain architecture (N-terminal HA-binding G1, C-terminal lectin/EGF/CRP G3) and revealed alternative splicing of two CS attachment domains, providing the structural framework for all subsequent isoform and domain studies.

    Evidence cDNA cloning, sequencing, and alternative splicing analysis

    PMID:8314802

    Open questions at the time
    • Functional differences between V0–V3 isoforms not yet defined
    • Ligand specificity of each domain not yet tested
  3. 1995 High

    Defined the genomic basis of isoform generation (exon VII/CS-α and exon VIII/CS-β), establishing how V0–V3 arise and why splicing controls glycosaminoglycan content.

    Evidence Genomic DNA analysis, Northern, cDNA sequencing, PCR, Southern blotting

    PMID:7730339 PMID:7876137

    Open questions at the time
    • Tissue-specific regulation of splicing not addressed
    • Phenotypic consequences of isoform loss not yet tested
  4. 1994 High

    Mapped the G3 domain's calcium-dependent C-type lectin and heparin-binding activities to the CRP-like module and identified versican as an anti-adhesive molecule regulating malignant adhesion phenotypes.

    Evidence GST-fusion expression, affinity chromatography, truncation mutagenesis; antisense suppression with adhesion/morphology readouts

    PMID:7531202 PMID:7961677

    Open questions at the time
    • In vivo relevance of lectin/heparin binding not established
    • Mechanism of anti-adhesion (steric vs signaling) unresolved
  5. 2000 High

    Demonstrated that V0/V1 isoforms promote directed neural crest migration via HNK-1-bearing surface components and that versican binds midkine/pleiotrophin through CS chains, linking versican to growth-factor presentation and guidance.

    Evidence In situ hybridization, orthotopic implantation, 3D migration assay, chondroitinase; affinity purification and Kd binding assays with chondroitinase controls

    PMID:10851128 PMID:10866805

    Open questions at the time
    • Identity of the HNK-1-bearing receptor not defined
    • Functional consequence of midkine binding in vivo not shown
  6. 2002 High

    Showed the G3 domain binds β1-integrin in a cation-dependent, non-RGD manner to activate FAK and confer apoptosis resistance, and that vascular isoforms promote platelet adhesion via dermatan sulfate, establishing versican as a signaling and hemostatic ligand.

    Evidence Pull-down, IP, FAK phosphorylation and apoptosis assays; platelet perfusion, GAG lyase digestion, affinity chromatography

    PMID:11805102 PMID:12468455

    Open questions at the time
    • Platelet-surface 120-140 kDa receptor not molecularly identified
    • Integrin signaling downstream of FAK not fully traced
  7. 2003 High

    Localized both HA and link protein binding to the G1 B-B' subdomain and established that G3 intermolecular disulfide bonds stabilize matrix and cell-matrix interactions, defining the structural basis of aggregate assembly.

    Evidence BIAcore SPR with recombinant subdomains and molecular modeling; non-reducing SDS-PAGE and reducing-agent functional assays

    PMID:12846582 PMID:12888576

    Open questions at the time
    • Stoichiometry of native aggregates in tissue not measured
    • Role of A subdomain in vivo not yet tested
  8. 2004 Medium

    Defined the G3 domain as a hub for tumor-promoting matrix signaling: it forms a fibronectin-VEGF trimeric complex driving angiogenesis, modulates EGFR-integrin crosstalk for anchorage-independent growth, and binds PSGL-1 to aggregate leukocytes.

    Evidence G3 and dominant-negative G3ΔEGF expression, co-IP of complexes, FAK/EGFR phosphorylation, soft agar and nude mouse tumor models, leukocyte aggregation assays

    PMID:14766798 PMID:15126624 PMID:15522894

    Open questions at the time
    • EGF motif requirement for secretion vs signaling not fully separated
    • Plasma versican fragment source not defined
  9. 2007 Medium

    Showed HA-versican aggregates, not free HA, drive stromal and endothelial infiltration, confirming the assembled complex as the angiogenic functional unit.

    Evidence Matrigel plug assay comparing aggregates vs native HA with histology

    PMID:17322391

    Open questions at the time
    • Receptor mediating aggregate-driven infiltration not identified
    • Contribution of specific isoform not resolved
  10. 1998 High

    Genetic disruption established versican as essential for endocardial cushion and right-ventricle formation, and later knock-in/knockout and exon-deletion models linked the G1 A subdomain and CS-rich isoforms to chondrogenesis, septal morphogenesis, and HA assembly/CD44-ERK-driven senescence.

    Evidence hdf insertional mutant, Cspg2Δ3/Δ3 and conditional Vcan knockout, exon 7 deletion mouse, antisense/chondroitinase/V3 overexpression with histology, migration, proliferation, ERK1/2 and senescence readouts

    PMID:16257955 PMID:16648631 PMID:19164294 PMID:22692047 PMID:24586547 PMID:9758703

    Open questions at the time
    • Distinct contributions of individual isoforms in vivo only partially separated
    • Mechanism coupling HA fragment-CD44 signaling to senescence not fully traced
  11. 2006 High

    Resolved the genetic and structural basis of Wagner vitreoretinopathy as a splicing imbalance disorder—intronic mutations shifting toward V2/V3 and one mutation abolishing an MMP cleavage site in GAGβ—rather than simple loss of function.

    Evidence Linkage analysis, Sanger sequencing, RT-PCR/qRT-PCR of isoforms in patient tissues; FRET-based proteolysis assay and structural modeling

    PMID:16877430 PMID:22739342 PMID:30657523

    Open questions at the time
    • How specific isoform ratio alters vitreous ECM mechanically not established
    • Tissue-to-tissue variability in isoform shift unexplained
  12. 2024 Medium

    Positioned VCAN as a convergent downstream effector of multiple oncogenic and fibrotic programs—Snail/PAPSS2, TGF-β1/FAP, ERK5, STAT5—and showed ADAMTS1 cleavage of V1 generates EGFR-transactivating fragments driving invasion and anoikis resistance.

    Evidence shRNA/overexpression epistasis and rescue, CHIP/luciferase, RTK arrays, co-IP, migration/invasion/anoikis assays, conditional knockout and xenograft/fibrosis mouse models

    PMID:29955124 PMID:37461061 PMID:39333870 PMID:39554845 PMID:39578365 PMID:39823128 PMID:40617369 PMID:41800245

    Open questions at the time
    • PI3K/AKT placement downstream of VCAN largely inferred from inhibitor studies
    • Some downstream pathways (CD44-Hippo-SP1, Twist1) rest on single-study Co-IP without orthogonal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How specific VCAN isoforms and their proteolytic fragments are selectively generated and read out by distinct receptors to produce context-dependent developmental versus disease outcomes remains unresolved.
  • No unifying model linking isoform/fragment identity to receptor choice
  • Receptors for several functional activities (platelet, HNK-1-mediated migration, aggregate infiltration) remain unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0098631 cell adhesion mediator activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 2 GO:0060089 molecular transducer activity 2
Localization
GO:0031012 extracellular matrix 5 GO:0005576 extracellular region 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 4
Partners
ADAMTS1CD44FN1HAPLN1ITGB1MDKSELPLGVEGF
Complex memberships
G3-fibronectin-VEGF trimeric complexversican-hyaluronan-link protein aggregate

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 PG-M (versican) binds directly to fibronectin and type I collagen, but not to laminin or type IV collagen, and mediates binding of hyaluronate to cellular fibronectin; the hyaluronate-binding activity in fibronectin preparations was immunoprecipitable with anti-PG-M antibody, demonstrating that PG-M is responsible for this activity. Immunoprecipitation, affinity purification, CsCl isopycnic centrifugation, binding assays The Journal of biological chemistry High 3759976
1986 PG-M (versican) is synthesized as the predominant large chondroitin sulfate proteoglycan in chick embryo limb buds before chondrogenesis, with a core protein of ~550 kDa, and its distribution closely follows mesenchymal cell condensation, suggesting a role in the condensation process. Metabolic labeling with [35S]sulfate, CsCl isopycnic centrifugation, SDS-PAGE, tryptic peptide mapping, immunofluorescence The Journal of biological chemistry Medium 3759975
1993 The PG-M/versican core protein contains an N-terminal hyaluronan-binding domain and C-terminal EGF-like domains, a C-type lectin-like domain, and a complement regulatory protein (CRP)-like domain, as deduced from cDNA sequence analysis; multiple alternatively spliced isoforms (V0, V1, V2, V3) are generated by alternative usage of two chondroitin sulfate attachment domains (CS-α and CS-β). cDNA cloning and sequencing, alternative splicing analysis, homology analysis The Journal of biological chemistry High 8314802
1994 The C-terminal (G3) domain of PG-M binds D-mannose, D-galactose, L-fucose, and N-acetyl-D-glucosamine in a calcium-dependent manner (C-type lectin activity), and also binds heparin/heparan sulfate; both activities require the intact CRP-like domain, as removal of this domain abolishes both C-type lectin and heparin binding activities. Expression of GST-fusion protein, affinity chromatography, truncation mutagenesis The Journal of biological chemistry High 7961677
1994 PG-M/versican acts as an anti-adhesive molecule; it is excluded from focal contacts of fibroblasts and from podosomes of osteosarcoma cells, and antisense-mediated suppression of PG-M/versican biosynthesis suppresses the malignant podosome-type adhesion phenotype of human osteosarcoma cells. Antisense inhibition, immunofluorescence localization, cell adhesion assays Journal of cell science Medium 7531202
1995 Multiple PG-M isoforms (V0 containing both CS-α and CS-β domains, V1 with CS-β only, V2 with CS-α only, and V3 with neither) are generated from a single genomic locus by alternative splicing of two large exons (exon VII encoding CS-α, 2880 bp; exon VIII encoding CS-β, 5229 bp); the V3 isoform lacks any chondroitin sulfate attachment region. Genomic DNA analysis, Northern hybridization, cDNA sequencing, PCR, Southern blotting The Journal of biological chemistry High 7730339 7876137
1998 Normal expression of the Cspg2 (versican) gene is required for formation of endocardial cushion swellings and the embryonic heart segments that give rise to the right ventricle and conus/truncus; hdf mice carrying a transgene insertional mutation disrupting Cspg2 die in utero by E10.5 and completely lack endocardial cushions and right cardiac chamber. Transgene insertional mutagenesis, chromosome mapping, immunohistochemistry, expression analysis (exon boundary PCR), genomic cloning Developmental biology High 9758703
2000 PG-M/versicans V0 and V1 isoforms are expressed along neural crest migratory pathways and promote directed (haptotactic) neural crest cell migration via HNK-1 antigen-bearing cell surface components; orthotopic implantation of PG-M/versican attracts migrating neural crest cells, whereas aggrecan retains them. Inhibitory effect of aggrecan on neural crest migration requires intact G1 domain-mediated association with cell-surface hyaluronan. In situ hybridization, immunohistochemistry, TEM/rotary shadowing, orthotopic microsphere implantation, 3D collagen migration assay, chondroitinase treatment Development (Cambridge, England) High 10851128
2000 PG-M/versican binds midkine (a heparin-binding growth factor) with Kd of 1.0 nM through the chondroitin sulfate chains; binding requires polysulfated regions and is abolished by chondroitinase ABC digestion; pleiotrophin binds similarly. Affinity purification, in-gel trypsin digestion/peptide sequencing, binding assay, chondroitinase digestion, competition with heparin/CS variants European journal of biochemistry Medium 10866805
2002 The C-terminal G3 domain of PG-M/versican binds β1-integrin in a calcium- and manganese-dependent manner (not via RGD motif); this interaction activates focal adhesion kinase, enhances integrin expression, promotes cell adhesion, and confers resistance to free radical-induced apoptosis. Pull-down assay, immunoprecipitation, cell-surface binding assay, native gel electrophoresis, FAK phosphorylation assay, apoptosis assay The Journal of biological chemistry High 11805102
2003 Versican/PG-M G1 domain binds both hyaluronan (HA) and link protein (LP); the B-B' subdomain of the G1 domain is sufficient for both HA and LP binding; the A subdomain enhances HA binding but has negligible effect on LP binding. A structural model of B-B' identifies deletion/insertion features critical for stable structure and HA binding. BIAcore surface plasmon resonance, recombinant subdomain expression, overlay sensorgrams, molecular modeling The Journal of biological chemistry High 12888576
2003 The G3 domains of PG-M/versican and aggrecan form intermolecular disulfide bonds involving all subdomains and all 10 cysteine residues; disruption of these disulfide bonds with reducing agents disrupts chondrocyte-matrix interaction, alters ECM structure, and reduces G3 domain-mediated cell adhesion. Recombinant protein expression, non-reducing SDS-PAGE, reducing agent treatment, chondrocyte-matrix interaction assay, cell adhesion assay Biochemistry Medium 12846582
2004 Versican G3 domain directly binds fibronectin and forms a trimeric complex with fibronectin and VEGF; this complex enhances endothelial cell adhesion, proliferation, and migration, and G3-expressing tumor cells show increased fibronectin and VEGF expression and enhanced angiogenesis in vivo. G3 construct expression in U87 cells, soft agarose colony assay, nude mouse tumor model, endothelial cell adhesion/proliferation/migration assays, co-immunoprecipitation of G3-fibronectin-VEGF complex FASEB journal High 14766798
2004 Versican G3 domain lacking EGF-like motifs (G3ΔEGF) acts as a dominant-negative, impairs versican secretion, enhances tumor cell adhesion, and prevents anchorage-independent growth. This mutant sustains FAK phosphorylation and integrin-EGFR association after serum withdrawal but reduces EGFR phosphorylation, demonstrating that the versican G3 domain modulates EGFR-integrin crosstalk to promote tumorigenesis. Dominant-negative G3ΔEGF transfection, FAK phosphorylation assay, co-immunoprecipitation of integrin-EGFR, soft agar growth assay Journal of cell science Medium 15126624
2004 PG-M/versican G3 domain binds P-selectin glycoprotein ligand-1 (PSGL-1); versican G3 multimers bridge PSGL-1-expressing leukocytes to induce leukocyte aggregation; endogenous G3-containing versican fragments in human plasma contribute to leukocyte aggregation, and removal of these fragments reduces the effect. Transfection, cell aggregation assay, PSGL-1 binding assays, human plasma depletion experiments, mouse model Journal of cell science Medium 15522894
2005 Versican/PG-M is required for mesenchymal condensation and chondrogenesis; chondrogenic stimuli upregulate V0 and V1 isoforms (containing more CS chains); antisense suppression of versican reduces chondrogenesis; chondroitinase ABC treatment or β-xyloside treatment (inhibiting CS chain addition to core proteins) suppresses chondrogenesis; forced expression of V3 (no CS chains) disrupts native versican organization and inhibits chondrogenesis. Antisense stable clones, chondroitinase ABC treatment, β-xyloside treatment, V3 overexpression, aggrecan deposition assay The Journal of biological chemistry High 16257955
2006 Versican/PG-M is present in articular cartilage as a proteoglycan aggregate with both link protein and hyaluronan (distinct from the aggrecan aggregate); its CS chains are predominantly nonsulfated (71%) and 4-sulfated (28%). Link protein overexpression enhances versican matrix deposition and prevents subsequent aggrecan deposition. Immunostaining, biochemical analysis of aggrecan-null (cmd/cmd) cartilage, chondroitinase ABC digestion/disaccharide analysis, link protein overexpression in N1511 cells The Journal of biological chemistry Medium 16648631
2006 Intronic mutations in CSPG2/VCAN at the splice acceptor site of intron 7 cause Wagner disease and erosive vitreoretinopathy by shifting the balance of splice variants: a >38-fold increase in V2 and >12-fold increase in V3 isoforms is consistently observed in patient tissues, representing a disease mechanism based on isoform imbalance rather than simple loss of function. Genetic linkage analysis, Sanger sequencing of CSPG2, RT-PCR of splice variants, quantitative RT-PCR (QPCR) in patient-derived tissues Investigative ophthalmology & visual science High 16877430
2007 Hyaluronan-versican aggregates (but not native hyaluronan alone) promote stromal cell recruitment and endothelial cell infiltration in Matrigel plug angiogenesis assays, indicating that the versican-HA complex is required for the pro-angiogenic activity. Matrigel plug assay, comparison of hyaluronan-versican aggregates vs. native HA, histological analysis of stromal/endothelial cell infiltration The American journal of pathology Medium 17322391
2009 Versican/PG-M is essential for assembling hyaluronan into extracellular matrix; knock-in mice (Cspg2Δ3/Δ3) lacking the A subdomain of the G1 domain show decreased versican and HA deposition, increased free HA fragments that interact with CD44, elevated ERK1/2 phosphorylation, and premature cellular senescence. Wild-type fibroblast treatment with hyaluronidase or exogenous HA enhances ERK1/2 phosphorylation via CD44; anti-CD44 antibody blocking inhibits this phosphorylation. Knock-in mouse model, ECM network immunofluorescence, anti-CD44 blocking antibody, ERK1/2 phosphorylation assay, senescence marker analysis (p53, p21, p16), exogenous HA/hyaluronidase treatment The Journal of biological chemistry High 19164294
2012 Versican/PG-M is required for ventricular septal formation subsequent to AV cushion development; Vcan knockout mice (Vcan Δ3/Δ3) show smaller AV cushions with narrowed ECM/cardiac jelly space, condensed HA without versican, and ventricular septal defects; ex vivo explant culture shows impaired cell migration in these regions. The A subdomain of the G1 domain is essential for proper proteoglycan aggregate formation and interventricular septal morphogenesis. Conditional Vcan knockout mouse, immunostaining, Ki67 proliferation assay, ex vivo collagen gel explant migration assay Glycobiology High 22692047
2012 Novel splice acceptor and donor-site mutations in VCAN (introns 7 and 8) cause Wagner syndrome through a pathogenic mechanism of increased transcript variants lacking exons 7 and/or 8, with reduction in glycosaminoglycan modifications; the magnitude of the isoform shift varies between tissues and mutations. Family-based genetic linkage, Sanger sequencing, qRT-PCR of isoforms in patient-derived venous blood and skin fibroblasts European journal of human genetics Medium 22739342
2014 Imbalanced expression of Vcan splice forms (deletion of exon 7 prevents V0 and V2 expression) results in ventricular septal defects, smaller valve cushions with diminished myocardialization, and altered outflow tracts; proteomic profiling of Vcan(tm1Zim) hearts identifies compensatory changes in cytoskeletal and muscle contraction proteins. Exon 7 deletion mouse model (Vcan(tm1Zim)), histology, large-scale differential protein expression profiling (proteomics) PloS one Medium 24586547
2019 A VCAN splice site mutation (c.4004-2A>G) eliminates an MMP cleavage site in the GAGβ chain (VCAN p.1335-1347 deletion), validated by FRET-based proteolysis assays; loss of this MMP cleavage site alters versican structure and results in abnormal vitreous ECM modeling, causing vitreoretinal degeneration. Sanger sequencing, protein structural modeling, FRET-based in vitro proteolysis assay, proteomic network analysis Investigative ophthalmology & visual science Medium 30657523
2018 Snail induces co-expression of PAPSS2 (rate-limiting enzyme in sulfation) and VCAN in breast cancer cells; depletion of VCAN dampens the cell migration activity induced by Snail or PAPSS2 in MCF 10A cells, establishing VCAN as a downstream effector in the Snail/PAPSS2 sulfation axis driving EMT and metastasis. shRNA knockdown, overexpression, cell migration assay, in vivo lung metastasis model (nude mice), PAPSS inhibitor (sodium chlorate) treatment Cell death and differentiation Medium 29955124
2002 Vascular PG-M/versican isoforms V1 and V2 promote platelet adhesion in a shear rate-dependent manner primarily through their dermatan sulfate chains; versicans incorporated into fibrillar collagen strongly promote platelet aggregation at both low and high shear rates; a 120-140 kDa polypeptide complex on the platelet surface serves as the versican-binding membrane ligand. Real-time platelet perfusion assay, glycosaminoglycan lyase digestion, competition with purified GAGs, affinity chromatography on DS-Sepharose, solid-phase binding assay FASEB journal Medium 12468455
2023 TGF-β1 derived from stromal fibroblasts upregulates FAP in fibroblasts, which in turn upregulates VCAN as a downstream molecule; VCAN plays an essential role in TGF-β1/FAP axis-induced EMT in bladder cancer cells potentially through PI3K/AKT1 signaling pathway. Primary CAF isolation, conditioned medium co-culture system, cytokine antibody array, gene set enrichment analysis, shRNA knockdown, cell migration/invasion assays Journal of translational medicine Low 37461061
2024 ADAMTS1 proteolytically cleaves versican V1 (VCAN V1), generating fragments that activate EGFR transactivation, which drives anoikis resistance and invasion in renal cell carcinoma; ADAMTS1 also forms a complex with p53 to modulate EGFR signaling. VCAN knockdown reverses ADAMTS1-induced pro-metastatic characteristics in vivo. RTK array screening, IP assays, luciferase reporter assays, western blotting, RT-qPCR, anoikis resistance assays, invasion assays, zebrafish xenotransplantation Cellular & molecular biology letters Medium 39333870
2025 STAT5 acts as a transcription factor that promotes VCAN expression upon bleomycin induction; elevated VCAN promotes fibroblast activation through the PI3K signaling pathway; fibroblast-specific VCAN knockout significantly reduces lung fibroblast activation and lung fibrosis in mice. Fibroblast-specific conditional VCAN knockout mice, Western blot, immunohistochemistry, immunofluorescence, chromatin immunoprecipitation (CHIP), luciferase reporter gene analysis, PI3K inhibitor treatment, bleomycin/radiation fibrosis models Cellular signalling Medium 40617369
2025 VCAN interacts with CD44 receptors on tumor-associated macrophages via paracrine secretion, promoting M2 macrophage polarization and VEGF-C secretion to facilitate lymphangiogenesis; VCAN also binds CD44 on gastric cancer cells via autocrine secretion, activating the Hippo pathway and upregulating SP1 to promote MIR181A2HG transcription, establishing a feedback loop. Co-IP, RNA-pulldown, luciferase reporter assay, CHIP, immunofluorescence, ELISA, in vitro and in vivo functional studies Cancer medicine Low 39823128
2024 VCAN is identified as a transcriptional target of ERK5 in soft tissue sarcoma; VCAN silencing phenocopies ERK5 silencing (impaired migration, adhesion, proliferation, tumorigenesis) and VCAN overexpression rescues ERK5 silencing phenotypes, confirming VCAN as an essential downstream mediator of ERK5-driven oncogenesis. shRNA silencing, overexpression, pharmacological ERK5 inhibition, migration/adhesion/proliferation/tumorigenesis assays, murine sarcoma model, transcriptomic profiling, human biopsy analysis (mRNA/protein) International journal of biological sciences Medium 41800245
2024 Versican promotes glioma cell proliferation and migration through the PI3K/Akt/AP-1 signaling pathway; PI3K/Akt pathway inhibition blocks VCAN-mediated glioma progression. VCAN overexpression in glioma cell lines, PI3K/Akt inhibitor treatment, functional proliferation and migration assays, transcriptomic analysis Frontiers in neuroscience Low 39554845
2025 Promoter hypomethylation (mediated by reduced DNA methyltransferase activity under hypoxia) upregulates versican expression; versican promotes endothelial-to-mesenchymal transition (EndMT) by targeting the transcription factor Twist1, driving pulmonary hypertension progression; endothelium-specific versican knockdown reverses HPH and prevents EndMT. Co-immunoprecipitation (versican-Twist1 interaction), Western blot, immunohistochemistry, immunofluorescence, methylation-specific PCR, endothelium-specific knockdown in mouse HPH model, hemodynamic measurements Journal of the American Heart Association Medium 39578365

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation. Developmental biology 270 9758703
1986 A large chondroitin sulfate proteoglycan (PG-M) synthesized before chondrogenesis in the limb bud of chick embryo. The Journal of biological chemistry 176 3759975
1995 Multiple forms of mouse PG-M, a large chondroitin sulfate proteoglycan generated by alternative splicing. The Journal of biological chemistry 157 7822336
1993 cDNA cloning of PG-M, a large chondroitin sulfate proteoglycan expressed during chondrogenesis in chick limb buds. Alternative spliced multiforms of PG-M and their relationships to versican. The Journal of biological chemistry 156 8314802
2004 Versican/PG-M G3 domain promotes tumor growth and angiogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 151 14766798
1986 Chondroitin sulfate proteoglycan (PG-M-like proteoglycan) is involved in the binding of hyaluronic acid to cellular fibronectin. The Journal of biological chemistry 143 3759976
2007 Hyperproduction of hyaluronan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment: possible involvement of versican/PG-M. The American journal of pathology 134 17322391
2003 Distinct interaction of versican/PG-M with hyaluronan and link protein. The Journal of biological chemistry 121 12888576
2000 Avian neural crest cell migration is diversely regulated by the two major hyaluronan-binding proteoglycans PG-M/versican and aggrecan. Development (Cambridge, England) 121 10851128
1995 Expression of PG-M(V3), an alternatively spliced form of PG-M without a chondroitin sulfate attachment in region in mouse and human tissues. The Journal of biological chemistry 113 7876137
2002 beta 1-Integrin-mediated glioma cell adhesion and free radical-induced apoptosis are regulated by binding to a C-terminal domain of PG-M/versican. The Journal of biological chemistry 112 11805102
2002 Distribution of PG-M/versican variants in human tissues and de novo expression of isoform V3 upon endothelial cell activation, migration, and neoangiogenesis in vitro. The Journal of biological chemistry 103 12221092
2018 Enhanced PAPSS2/VCAN sulfation axis is essential for Snail-mediated breast cancer cell migration and metastasis. Cell death and differentiation 98 29955124
1996 2B1 antigen characteristically expressed on extracellular matrices of human malignant tumors is a large chondroitin sulfate proteoglycan, PG-M/versican. Cancer research 91 8752156
1994 Repression of a malignant cell-substratum adhesion phenotype by inhibiting the production of the anti-adhesive proteoglycan, PG-M/versican. Journal of cell science 91 7531202
1993 Tissue variation of two large chondroitin sulfate proteoglycans (PG-M/versican and PG-H/aggrecan) in chick embryos. Anatomy and embryology 84 8342790
1997 Immunohistochemical localization of extracellular matrix components in human breast tumours with special reference to PG-M/versican. The Histochemical journal 81 9088942
1996 Inhibitory effects of PG-H/aggrecan and PG-M/versican on avian neural crest cell migration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 78 8641562
1999 Versican/PG-M isoforms in vascular smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology 74 10397680
2012 Versican/PG-M is essential for ventricular septal formation subsequent to cardiac atrioventricular cushion development. Glycobiology 69 22692047
2000 A heparin-binding growth factor, midkine, binds to a chondroitin sulfate proteoglycan, PG-M/versican. European journal of biochemistry 67 10866805
2006 Erosive vitreoretinopathy and wagner disease are caused by intronic mutations in CSPG2/Versican that result in an imbalance of splice variants. Investigative ophthalmology & visual science 66 16877430
2004 PG-M/versican binds to P-selectin glycoprotein ligand-1 and mediates leukocyte aggregation. Journal of cell science 63 15522894
2005 Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome. Investigative ophthalmology & visual science 62 16043844
1992 Mapping of the versican proteoglycan gene (CSPG2) to the long arm of human chromosome 5 (5q12-5q14). Genomics 59 1478664
2004 The globular domains of PG-M/versican modulate the proliferation-apoptosis equilibrium and invasive capabilities of tumor cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 56 14977887
2005 Versican/PG-M regulates chondrogenesis as an extracellular matrix molecule crucial for mesenchymal condensation. The Journal of biological chemistry 55 16257955
1995 The gene structure and organization of mouse PG-M, a large chondroitin sulfate proteoglycan. Genomic background for the generation of multiple PG-M transcripts. The Journal of biological chemistry 51 7730339
2023 TGF-β1 dominates stromal fibroblast-mediated EMT via the FAP/VCAN axis in bladder cancer cells. Journal of translational medicine 49 37461061
2004 Overexpression of the C-terminal PG-M/versican domain impairs growth of tumor cells by intervening in the interaction between epidermal growth factor receptor and beta1-integrin. Journal of cell science 48 15126624
1996 Distinct rat aortic smooth muscle cells differ in versican/PG-M expression. Arteriosclerosis, thrombosis, and vascular biology 48 8640411
2006 Identification and characterization of versican/PG-M aggregates in cartilage. The Journal of biological chemistry 47 16648631
1994 Expression and binding activity of the carboxyl-terminal portion of the core protein of PG-M, a large chondroitin sulfate proteoglycan. The Journal of biological chemistry 43 7961677
2009 Versican/PG-M Assembles Hyaluronan into Extracellular Matrix and Inhibits CD44-mediated Signaling toward Premature Senescence in Embryonic Fibroblasts. The Journal of biological chemistry 42 19164294
2019 Long noncoding RNA VCAN-AS1 contributes to the progression of gastric cancer via regulating p53 expression. Journal of cellular physiology 39 31637706
2012 Novel VCAN mutations and evidence for unbalanced alternative splicing in the pathogenesis of Wagner syndrome. European journal of human genetics : EJHG 35 22739342
2017 MiR-135a-5p modulates biological functions of thyroid carcinoma cells via targeting VCAN 3'-UTR. Cancer biomarkers : section A of Disease markers 34 28869452
1996 Deposition of PG-M/versican is a major cause of human coronary restenosis after percutaneous transluminal coronary angioplasty. The Journal of pathology 34 8958811
1999 Refined genetic and physical localization of the Wagner disease (WGN1) locus and the genes CRTL1 and CSPG2 to a 2- to 2.5-cM region of chromosome 5q14.3. Genomics 33 10198161
2002 Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 12468455
1997 Transient expression of PG-M/versican, a large chondroitin sulfate proteoglycan in developing chicken retina. Journal of neurochemistry 31 9349562
1995 Expression pattern and mapping of the murine versican gene (Cspg2) to chromosome 13. Genomics 31 8530092
2021 INHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN. The Journal of international medical research 30 34130530
2019 Up-regulation of EMT-related gene VCAN by NPM1 mutant-driven TGF-β/cPML signalling promotes leukemia cell invasion. Journal of Cancer 28 31777586
2008 Complex t(5;8) involving the CSPG2 and PTK2B genes in a case of dermatofibrosarcoma protuberans without the COL1A1-PDGFB fusion. Virchows Archiv : an international journal of pathology 28 18253748
2020 VUp-Regulation of VCAN Promotes the Proliferation, Invasion and Migration and Serves as a Biomarker in Gastric Cancer. OncoTargets and therapy 26 32922041
2011 A new VCAN/versican splice acceptor site mutation in a French Wagner family associated with vascular and inflammatory ocular features. Molecular vision 26 21738396
2014 Association of Versican (VCAN) gene polymorphisms rs251124 and rs2287926 (G428D), with intracranial aneurysm. Meta gene 24 25606449
2009 Mutational hot spot potential of a novel base pair mutation of the CSPG2 gene in a family with Wagner syndrome. Archives of ophthalmology (Chicago, Ill. : 1960) 24 19901218
2020 The circ_VCAN with radioresistance contributes to the carcinogenesis of glioma by regulating microRNA-1183. Medicine 20 32080097
2019 VCAN Canonical Splice Site Mutation is Associated With Vitreoretinal Degeneration and Disrupts an MMP Proteolytic Site. Investigative ophthalmology & visual science 20 30657523
2014 Imbalanced expression of Vcan mRNA splice form proteins alters heart morphology and cellular protein profiles. PloS one 20 24586547
2024 Collagen I-induced VCAN/ERK signaling and PARP1/ZEB1-mediated metastasis facilitate OSBPL2 defect to promote colorectal cancer progression. Cell death & disease 19 38267463
2021 miR-543 impairs cell proliferation, migration, and invasion in breast cancer by suppressing VCAN. Biochemical and biophysical research communications 19 34293593
2021 Long non-coding RNA VCAN-AS1 promotes the malignant behaviors of breast cancer by regulating the miR-106a-5p-mediated STAT3/HIF-1α pathway. Bioengineered 19 34365889
1994 Abnormal occurrence of a large chondroitin sulfate proteoglycan, PG-M/versican in osteoarthritic cartilage. Osteoarthritis and cartilage 18 11548223
2005 Expression of a chondroitin sulfate proteoglycan, versican (PG-M), during development of rat cornea. Current eye research 16 16020278
1999 Genetic analysis of steel and the PG-M/versican-encoding gene AxPG as candidates for the white (d) pigmentation mutant in the salamander Ambystoma mexicanum. Development genes and evolution 16 10370116
2003 G3 domains of aggrecan and PG-M/versican form intermolecular disulfide bonds that stabilize cell-matrix interaction. Biochemistry 15 12846582
2006 Involvement of tenascin-C and PG-M/versican in flexor tenosynovial pathology of idiopathic carpal tunnel syndrome. Histology and histopathology 14 16493581
2021 Circular RNA Circ-0002570 Accelerates Cancer Progression by Regulating VCAN via MiR-587 in Gastric Cancer. Frontiers in oncology 13 34692507
2015 The Bacterial Component Flagellin Induces Anti-Sepsis Protection Through TLR-5, IL-1RN and VCAN During Polymicrobial Sepsis in Mice. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 13 25968570
2018 Is exon 8 the most critical or the only dispensable exon of the VCAN gene? Insights into VCAN variants and clinical spectrum of Wagner syndrome. American journal of medical genetics. Part A 12 30055036
1997 PG-M/versican-like proteoglycans are components of large disulfide-stabilized complexes in the axolotl embryo. The Journal of biological chemistry 12 9013561
2022 JAM-A facilitates hair follicle regeneration in alopecia areata through functioning as ceRNA to protect VCAN expression in dermal papilla cells. Precision clinical medicine 11 36132055
2022 VCAN, expressed highly in hepatitis B virus-induced hepatocellular carcinoma, is a potential biomarker for immune checkpoint inhibitors. World journal of gastrointestinal oncology 10 36310697
2023 VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma. International journal of molecular sciences 9 37108649
2010 The intracranial aneurysm susceptibility genes HSPG2 and CSPG2 are not associated with abdominal aortic aneurysm. Angiology 9 20053631
2001 Age differences in immunohistochemical localizations of large proteoglycan, PG-M/versican, and small proteoglycan, decorin, in the dermis of rats. Experimental animals 9 11381620
1997 Reduced epidermal expression of a PG-M/versican-like proteoglycan in embryos of the white mutant axolotl. Experimental cell research 9 9344585
2022 Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis. Frontiers in molecular biosciences 8 36275632
2020 Semen Modulates the Expression of NGF, ABHD2, VCAN, and CTEN in the Reproductive Tract of Female Rabbits. Genes 8 32645906
2007 Chondroitin sulfate proteoglycan 2 (CSPG2) gene polymorphisms rs173686 and rs251124 are not associated with intracranial aneurysms in Chinese Han nationality. Upsala journal of medical sciences 8 18484070
2024 The oncogenic ADAMTS1-VCAN-EGFR cyclic axis drives anoikis resistance and invasion in renal cell carcinoma. Cellular & molecular biology letters 7 39333870
2025 The MIR181A2HG/miR-5680/VCAN-CD44 Axis Regulates Gastric Cancer Lymph Node Metastasis by Promoting M2 Macrophage Polarization. Cancer medicine 6 39823128
2020 Identification of Novel Copy Number Variations of VCAN Gene in Three Chinese Families with Wagner Disease. Genes 6 32854301
2023 MiRNA-30a-5p/VCAN Arrests Tumor Metastasis via Modulating the Adhesion of Lung Adenocarcinoma Cells. Applied biochemistry and biotechnology 5 37032373
1998 Differentiation of EL4 lymphoma cells by tumoral environment is associated with inappropriate expression of the large chondroitin sulfate proteoglycan PG-M and the tumor-associated antigen HTgp-175. International journal of cancer 5 9797141
2024 Promotor Hypomethylation Mediated Upregulation of VCAN Targets Twist1 to Promote EndMT in Hypoxia-Induced Pulmonary Hypertension. Journal of the American Heart Association 4 39578365
2023 DSE inhibits melanoma progression by regulating tumor immune cell infiltration and VCAN. Cell death discovery 4 37833287
2025 Revealing VCAN as a Potential Common Diagnostic Biomarker of Renal Tubules and Glomerulus in Diabetic Kidney Disease Based on Machine Learning, Single-Cell Transcriptome Analysis and Mendelian Randomization. Diabetes & metabolism journal 3 39849979
2025 Resveratrol suppresses growth and VCAN expression in a Cancer-associated fibroblast-breast Cancer hybrid organoid. International immunopharmacology 3 40101422
2025 Indole-3-lactic acid derived from tryptophan metabolism promotes trophoblast migration and invasion by activating the AhR/VCAN pathway. Placenta 3 40153926
2025 STAT5/VCAN/PI3K signaling pathway promotes fibroblast activation and lung fibrosis. Cellular signalling 3 40617369
2024 VCAN in the extracellular matrix drives glioma recurrence by enhancing cell proliferation and migration. Frontiers in neuroscience 3 39554845
2024 Long non-coding RNA VCAN-AS1 promotes gastric cancer progression via the HuR/F11R pathway. American journal of translational research 3 39678543
2023 COL3A1, CXCL8, VCAN, THBS2, and COL1A2 are correlated with the onset of biliary atresia. Medicine 3 36930067
2023 Pan-cancer analysis of the oncogenic role of the core osteosarcoma gene VCAN in human tumors. American journal of translational research 3 37854213
2022 Downregulation of miR-23a-3p improves cognitive function in rats after subarachnoid hemorrhage by targeting VCAN. Medical molecular morphology 3 35137264
2022 A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy. Molecular genetics & genomic medicine 3 36333947
2021 Expression of VCAN and its receptors in canine mammary carcinomas with or without myoepithelial proliferation. Research in veterinary science 3 34399281
2013 [Association of single nucleotide polymorphisms of CSPG2 and HSPG2 genes with intracranial aneurysm in ethnic Han Chinese population]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 3 23568740
2023 Sevoflurane Exposure of Clinical Doses in Pregnant Rats Induces Vcan Changes without Significant Neural Apoptosis in the Offspring. Medicina (Kaunas, Lithuania) 2 36837392
2022 Multimodal Retinal Imaging Findings in Two Cousins With VCAN-Related Vitreoretinopathy or Wagner Disease. Ophthalmic surgery, lasers & imaging retina 2 36378611
2019 The Association between Genes Polymorphisms of Heparan Sulfate Proteoglycan 2 (HSPG2) and Chondroitin Sulfate Proteoglycan 2 (CSPG2) and Intracranial Aneurysm Susceptibility: A Meta-Analysis. Iranian journal of public health 2 31970092
2026 Bulk Sequencing Combined With Single-Cell Sequencing Identifies High Expression of VCAN in Fibroblasts Promoting the Progression of High-Stemness Gastric Adenocarcinoma Cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41555841
2026 Trichosanthes kirilowii extract alleviated liver fibrosis and acute myocardial infarction by inhibiting VCAN to restrain monocyte senescence: Insights from bioinformatic analyses and experimental validation. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41720002
2026 VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma. International journal of biological sciences 0 41800245
2025 Visfatin facilitates esophageal cancer migration by suppressing miR‑3613‑5p expression and promoting VEZF1/VCAN production. Oncology reports 0 40747711
2024 Clinical significance and potential pathogenesis of VCAN in adult non-cystic fibrosis bronchiectasis: a retrospective study. BMC pulmonary medicine 0 38685004

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