Affinage

SDC4

Syndecan-4 · UniProt P31431

Length
198 aa
Mass
21.6 kDa
Annotated
2026-06-10
54 papers in source corpus 25 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SDC4 (syndecan-4/amphiglycan/ryudocan) is a type I transmembrane heparan sulfate proteoglycan that couples extracellular matrix engagement to intracellular signaling, governing cell adhesion, migration, mechanosensing, and proliferation (PMID:1500433, PMID:29033837). Its core protein carries three glycosaminoglycan attachment sites (Ser-44, Ser-65, Ser-67), each independently capable of bearing heparan sulfate or chondroitin sulfate, generating compositionally diverse isoforms (PMID:7520439), and its heparan sulfate chains mediate high-affinity binding to basic FGF, midkine, and tissue factor pathway inhibitor (PMID:8621465). Through its cytoplasmic and transmembrane domains SDC4 nucleates signaling: it cooperates with integrin-β1 and integrin-αvβ1 to engage fibronectin in a FAK/PI3K-Akt-dependent manner that supports cell adhesion and survival (PMID:31111299, PMID:40747330), and drives migration through a PKCα–Src–FAK–ERK1/2 cascade (PMID:29033837) as well as RhoA/ROCK-mediated cytoskeletal reorganization and amoeboid motility (PMID:41783041, PMID:42017444). SDC4 acts as a receptor for pleiotrophin in cardiac fibroblasts and macrophages and in directed neural invasion (PMID:39765325, PMID:42017444), and its surface abundance is enhanced by MALL-dependent recycling to the plasma membrane (PMID:42017444). SDC4 transcription is directly induced by NF-κB downstream of TNF-α and IL-1β, by KLF5, and by HOXB9 under ischemic conditions (PMID:40341546, PMID:41534677, PMID:41747442, PMID:40571266), while its mRNA is destabilized by ZFP36L1 acting on 3'UTR AU-rich elements within a TGF-β positive feedback loop (PMID:37935976). SDC4 supports proliferation by modulating cell-cycle machinery at the G1/S restriction point (PMID:41890271) and is required for macropinocytosis in pancreatic cancer (PMID:35812066). Global Sdc4 knockout in mice reveals roles in vertebral bone homeostasis, intervertebral disc matrix regulation, and load-induced disc remodeling (PMID:38806135, PMID:41053113).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 High

    Establishing SDC4 as a distinct cell-surface heparan sulfate proteoglycan defined the molecular entity and its domain architecture, separating it from related syndecan-family members.

    Evidence Molecular cloning, antibody generation against fusion protein, and immunostaining of human lung fibroblasts

    PMID:1500433

    Open questions at the time
    • Function of the conserved cytoplasmic tyrosines not yet tested
    • No ligand or signaling partner identified
  2. 1993 High

    Independent cloning of the human and rat core proteins confirmed the type I membrane topology, three GAG attachment regions, and conserved cytoplasmic domains, and localized the gene to 20q12.

    Evidence cDNA cloning, sequence analysis, FISH, and protein purification with peptide mapping in endothelial cells

    PMID:7916598 PMID:8495865

    Open questions at the time
    • GAG attachment sites inferred, not functionally mapped
    • No functional role for the conserved cytoplasmic domain established
  3. 1994 High

    Site-directed mutagenesis resolved which serines bear GAG chains and showed each site can carry either HS or CS, explaining the structural basis of SDC4 isoform diversity.

    Evidence Stable transfection of epitope-tagged constructs with Ser→Thr mutagenesis, GAG lyase digestion in mouse L cells

    PMID:7520439

    Open questions at the time
    • Functional consequences of HS vs CS substitution not addressed
    • Determinants selecting HS over CS unknown
  4. 1996 High

    Demonstrating that purified SDC4 HS chains bind bFGF, midkine, and TFPI with nanomolar affinity assigned the proteoglycan a concrete ligand-capture function.

    Evidence Purified protein, solid-phase binding with heparitinase/chondroitinase dissection and competition assays

    PMID:8621465

    Open questions at the time
    • Downstream signaling consequences of ligand binding not tested
    • Cell-type specificity of HS fine structure not resolved
  5. 1996 Medium

    Defining the human and mouse gene structure and proximal promoter elements provided the framework for understanding transcriptional control of SDC4.

    Evidence Genomic cloning, sequencing, and luciferase reporter/promoter deletion analysis

    PMID:8797100 PMID:9276666

    Open questions at the time
    • Predicted transcription factor sites (NF-κB, Sp1, AP-2) not yet validated by direct binding
    • Physiological inducers of transcription unknown
  6. 2019 Medium

    Showing that SDC4 partners with integrin-β1 to engage fibronectin through FAK/PI3K-Akt linked the proteoglycan to adhesion-dependent survival signaling and anoikis control.

    Evidence Immunofluorescence, western blotting, and FAK activity assays in nucleus pulposus cells with TNF-α perturbation

    PMID:31111299

    Open questions at the time
    • Direct SDC4-integrin contact not biophysically demonstrated here
    • Single cell type
  7. 2021 Medium

    Loss-of-function across multiple cancer models established that SDC4 drives migration, invasion, EMT, and proliferation through PKCα/Src/FAK/ERK and Wnt/β-catenin signaling.

    Evidence shRNA/siRNA knockdown, epistasis (si-β-catenin rescue), Co-IP of SDC4/DDX23, migration and proliferation assays across hepatic, thyroid, and HCC cells

    PMID:29033837 PMID:30165731 PMID:33990545

    Open questions at the time
    • Whether SDC4 acts via HS chains or cytoplasmic domain in these pathways not dissected
    • DDX23 interaction is a single Co-IP context
  8. 2022 Medium

    CRISPR knockout in pancreatic cancer revealed a requirement for SDC4 in macropinocytosis and tumor growth, and identified its transmembrane motif as essential for small-molecule binding.

    Evidence CRISPR/Cas9 knockout, quantitative proteomics, ligand binding (Kd) measurement, transmembrane mutagenesis, xenograft assays

    PMID:35812066

    Open questions at the time
    • Mechanism connecting SDC4 to macropinocytic machinery unresolved
    • Single cancer context
  9. 2024 Medium

    Global knockout in mice assigned SDC4 in vivo roles in vertebral bone mass, biomechanics, and intervertebral disc matrix composition, including HS/CS balance.

    Evidence Global Sdc4 knockout, micro-CT, histology, FTIR imaging, and transcriptomics

    PMID:38806135

    Open questions at the time
    • Cell-type responsible for bone phenotype (osteoclast vs osteoblast) not pinned down
    • Mechanistic link to GAG-degradation transcriptomic signature untested
  10. 2025 Medium

    Direct ChIP/reporter evidence established NF-κB, KLF5, and HOXB9 as transcriptional activators of SDC4 in inflammatory, cancer, and ischemic contexts, defining how SDC4 levels are set.

    Evidence ChIP-qPCR, dual-luciferase reporter assays, pharmacological NF-κB inhibition across endothelial, colorectal, and esophageal cells

    PMID:40341546 PMID:40571266 PMID:41534677 PMID:41747442

    Open questions at the time
    • Combinatorial vs context-specific use of these factors unresolved
    • Each factor demonstrated in a single cell system
  11. 2025 Medium

    Identifying ZFP36L1-mediated 3'UTR decay within a TGF-β feedback loop, and a TGF-β/TGFBR3 protective axis, added post-transcriptional control of SDC4 abundance.

    Evidence ZFP36L1 perturbation, ARE mutation, RNA stability assays, MMP/TGF-β inhibitors, in vivo metastasis model

    PMID:37935976

    Open questions at the time
    • Generality of the feedback loop beyond osteosarcoma unknown
  12. 2025 Medium

    Proximity ligation confirmed an extracellular SDC4-integrin-αvβ1 interaction transmitting fibrotic ECM stiffness into FAK/AKT, PKCα, and TGF-β signaling, and identified pleiotrophin as an SDC4 receptor ligand in cardiac disease.

    Evidence Decellularized ECM model, Duolink-PLA, blocking antibody/interfering peptide, AlphaFold2-Multimer docking; PTN ligand validated by functional assays and TAC mouse model

    PMID:39765325 PMID:40747330

    Open questions at the time
    • Stoichiometry of SDC4-integrin complex not defined
    • Whether PTN binds HS chains or core protein not specified
  13. 2026 Medium

    Recent work positioned SDC4 as a RhoA/ROCK effector controlling actin reorganization, amoeboid motility, perineural invasion, antiviral cell-cell barrier formation, cell-cycle control, and secretory granule biogenesis, revealing diverse cytoplasmic-domain functions.

    Evidence Pathway epistasis (TNFR1-MAPK-SDC4-RhoA/ROCK), Co-IP of MALL and IP6K1, surface trafficking assays, AAV knockdown in KPC mice, cell-cycle/anoikis flow cytometry

    PMID:41783041 PMID:41890271 PMID:42017444 PMID:42053465

    Open questions at the time
    • How a single proteoglycan integrates these divergent outputs unclear
    • Each output demonstrated in a distinct cell system without unifying mechanism

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SDC4 HS-chain composition, core-protein/integrin contacts, and cytoplasmic-domain signaling are integrated to specify context-dependent outputs, and which functions depend on GAG chains versus protein-protein interactions.
  • No structure of full-length SDC4 or its signaling complexes
  • GAG-dependent vs GAG-independent functions not systematically separated
  • No timeline evidence linking SDC4 to a defined Mendelian disease

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1640170 Cell Cycle 1
Partners
DDX23FN1IP6K1ITGAVITGB1MALLPTNTGFBR3

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 SDC4 (amphiglycan) was identified as a novel integral membrane heparan sulfate proteoglycan with discrete cytoplasmic, transmembrane, and extracellular domains. The transmembrane and cytoplasmic domains are highly similar to fibroglycan and syndecan, including conservation of four tyrosine residues and conserved proximal/distal cytoplasmic sequences. Polyclonal and monoclonal antibodies against the encoded peptide (expressed as a beta-galactosidase fusion protein) confirmed it as a 35-kD core protein cell surface HSPG on human lung fibroblasts. Molecular cloning, antisense oligonucleotide-primed PCR, antibody generation against fusion protein, immunostaining The Journal of cell biology High 1500433
1993 SDC4 (ryudocan) core protein was cloned from human endothelial cells; the deduced sequence encodes a 198 amino acid type I integral membrane protein with conserved transmembrane/cytoplasmic domains containing four tyrosine groups and three glycosaminoglycan (GAG) chain attachment regions. The gene was chromosomally localized to 20q12 by fluorescence in situ hybridization. cDNA cloning, sequence analysis, fluorescence in situ hybridization (FISH) Biochemical and biophysical research communications High 7916598
1993 SDC4 (ryudocan) isolated from rat endothelial cells bears heparan sulfate chains; its core protein is a type I integral membrane protein of 202 amino acids with homologous transmembrane and intracellular domains to syndecan but a distinct extracellular region with only 3 potential GAG attachment sites. Both ryudocan and syndecan mRNAs are abundantly expressed in microvascular endothelial cells and associated non-endothelial cells. Ion-exchange chromatography, affinity fractionation, SDS-PAGE, peptide mapping, N-terminal sequencing, PCR, cDNA isolation, quantitative PCR Haemostasis High 8495865
1994 SDC4 (ryudocan) possesses three functional GAG attachment sites at Ser-44, Ser-65, and Ser-67. Each site can independently bear either heparan sulfate or chondroitin sulfate, generating multiple isoforms (pure HS, mixed HS/CS hybrids, pure CS). Ser→Thr mutations at all three positions prevented GAG attachment. The promiscuity of GAG attachment is encoded in the core protein structure. Stable transfection of epitope-tagged ryudocan constructs in mouse L cells, site-directed mutagenesis (Ser→Thr), immunopurification, GAG lyase digestion, SDS-PAGE The Journal of biological chemistry High 7520439
1996 Human SDC4 (ryudocan) purified from endothelium-like EAhy926 cells bears only heparan sulfate (HS) chains on a ~30 kDa core protein. Its HS chains are responsible for binding basic FGF (Kd ~0.50 nM), midkine (Kd ~0.30 nM), and tissue factor pathway inhibitor (TFPI; Kd ~0.74 nM) as demonstrated by heparitinase (but not chondroitin ABC lyase) abrogation of binding, and competition with heparin/HS but not chondroitin sulfate. Protein purification (ion-exchange + immunoaffinity chromatography), solid-phase binding assay, heparitinase and chondroitin ABC lyase treatment, competition assays The Journal of biological chemistry High 8621465
1996 The human SDC4 (ryudocan) gene spans ~24 kb and is divided into five exons. Exon I encodes the signal peptide; exons II–IV the extracellular domain; exon V the transmembrane and cytoplasmic domains (highly homologous among syndecan family members). The 5'-flanking region contains a TATA-like sequence and binding sites for multiple transcription factors (Sp1, AP-2, NF-κB, etc.) and functions as a promoter in transfection assays. Genomic library screening, restriction mapping, sequencing, primer extension, transient transfection/luciferase reporter assay Journal of biochemistry Medium 8797100
1997 The mouse SDC4 (ryudocan) gene spans ~19.7 kb with five exons in an intron-exon organization identical to the human gene. The proximal promoter region including a TATA-like box, GC box, and Sp1 binding sites is required for full transcriptional activity, as shown by deletion analysis of a luciferase reporter construct. Genomic DNA cloning, sequencing, Northern analysis, transient transfection with luciferase reporter, promoter deletion analysis Journal of biochemistry Medium 9276666
2017 SDC4 knockdown by shRNA in HSC-T6 cells blocked cell migration. SDC4 acts through a signaling pathway involving PKCα, Src, FAK, and ERK1/2 as well as fibronectin (Fn). Dioscin inhibited HSC-T6 migration by downregulating SDC4 and its downstream pathway components. iTRAQ-based quantitative proteomics, shRNA knockdown, wound-healing assay, transwell migration assay, western blotting Frontiers in pharmacology Medium 29033837
2018 SDC4 gene silencing in human papillary thyroid carcinoma cells suppressed cell migration, invasion, and epithelial-mesenchymal transition (EMT), and promoted apoptosis by inhibiting the Wnt/β-catenin signaling pathway. Conversely, si-β-catenin inhibited the pro-migratory and invasive effects of SDC4 overexpression, placing SDC4 upstream of β-catenin in this pathway. siRNA silencing, overexpression, Transwell assay, scratch test, flow cytometry, western blotting, epistasis (si-β-catenin rescue of SDC4 overexpression phenotype) Molecules and cells Medium 30165731
2019 In nucleus pulposus cells, integrin β1 (ITGβ1) and SDC4 work synergistically to engage fibronectin (FN) in a focal adhesion kinase (FAK)-dependent fashion. TNF-α treatment weakened FAK activity and downstream PI3K/Akt phosphorylation, reducing adherence capacity and increasing anoikis. TNF-α thus disrupts the FN/ITGβ1/SDC4 complex and associated survival signaling. Immunofluorescent staining, western blotting, RT-PCR, dual-mode FAK activity detection, PI3K/Akt pathway analysis Inflammation Medium 31111299
2021 SDC4 directly binds bufalin (small molecule) and selectively increases SDC4 interaction with DDX23, inducing genomic instability in HCC cells. The SDC4/DDX23 complex formation also inactivates matrix metalloproteinases (MMPs) and augments p38/JNK MAPK phosphorylation. Specific knockdown of SDC4 or DDX23 abolished bufalin-dependent inhibition of HCC proliferation and migration. Target identification (cellular protein-ligand binding), Co-IP, western blotting, siRNA knockdown of SDC4 and DDX23, proliferation and migration assays Cell death & disease Medium 33990545
2022 SDC4 knockout in pancreatic cancer cells markedly impaired macropinocytosis, colony formation, and xenograft tumor growth. Eltrombopag (ETBP) directly binds SDC4 with a Kd ~2 µM; the transmembrane motif is essential for this binding. ETBP increases SDC4 abundance and enhances SDC4-associated MAPK signaling and macropinocytosis in cancer cells. CRISPR/Cas9 knockout, quantitative proteomics, cellular protein-based ligand interaction screening, binding affinity measurement (Kd), mutagenesis of transmembrane motif, xenograft assays American journal of cancer research Medium 35812066
2023 ZFP36L1 regulates SDC4 mRNA decay through AU-rich elements (AREs) in the SDC4 3'UTR. SDC4 protects TGFBR3 from MMP-mediated cleavage, relieving inhibition of TGF-β signaling by soluble TGFBR3. TGF-β signaling in turn positively regulates SDC4 transcription, forming a positive feedback loop between SDC4 and TGF-β signaling that promotes osteosarcoma cell migration. ZFP36L1 knockdown/overexpression, ARE mutation in SDC4 3'UTR, TGF-β pathway inhibitors, MMP inhibition, in vivo lung metastasis model, RNA stability assays Oncogene Medium 37935976
2024 Global Sdc4 knockout in mice caused severely reduced vertebral trabecular and cortical bone mass with altered biomechanical properties, likely due to elevated osteoclastic activity. Sdc4 deletion also altered intervertebral disc matrix, reducing mature collagen crosslinks in nucleus pulposus and annulus fibrosus, and increasing chondroitin sulfate in the nucleus pulposus. Transcriptomic analysis showed dysregulation of heparan sulfate GAG degradation, mitochondrial metabolism, autophagy, and ER-associated protein processing. Global knockout mouse model, micro-CT, histology, Imaging-FTIR, transcriptomic analysis (CompBio AI tool) Matrix biology : journal of the International Society for Matrix Biology Medium 38806135
2025 Sdc4 knockout mice subjected to altered spinal loading (Ca3-6 flexion) did not exhibit increased collagen fibril and fibronectin deposition in the nucleus pulposus compartment, nor alterations in collagen crosslinks, fibroblastic COL10 deposition, or loss of notochordal (transgelin+) cell characteristics seen in wild-type mice. Proteomic analysis revealed that SDC4-KO NP cells showed increased dynamin-mediated endocytosis and autophagy-related pathway activity. Sdc4 global KO mice, histology, collagen crosslink analysis, immunostaining, quantitative proteomics Cell death & disease Medium 41053113
2025 HOXB9 acts as a transcription factor that directly binds the SDC4 promoter (site 2) to induce SDC4 transcription in endothelial cells under ischemic (OGD/R) conditions. SDC4 overexpression promoted PKCα activation and reduced tight junction protein expression, impairing blood-brain barrier integrity. SDC4 interference mitigated BBB disruption and neuroinflammation in vivo. ChIP assay, dual-luciferase reporter assay, siRNA knockdown, overexpression, TEER assay, Evans Blue assay, immunofluorescence, MCAO rat model Brain research bulletin Medium 40571266
2025 SDC4 is a direct transcriptional target of NF-κB. TNF-α treatment drives NF-κB binding to the SDC4 promoter (a region enriched for active chromatin mark H3K27Ac), upregulating SDC4 mRNA and protein. The NF-κB inhibitor Bay11-7082 blocked TNF-α-induced NF-κB nuclear translocation and SDC4 upregulation. ChIP-qPCR, qRT-PCR, western blotting, immunofluorescence, pharmacological NF-κB inhibition, UCSC genome browser analysis Scientific reports Medium 40341546
2025 KLF5 transcription factor directly binds two regions near positions -70 to -40 of the SDC4 promoter, as confirmed by promoter reporter assay and ChIP-qPCR. This binding is necessary for full SDC4 promoter activity in colorectal cancer cells. Bioinformatics, promoter/luciferase reporter assay, ChIP-qPCR, immunohistochemistry Biochemical and biophysical research communications Medium 41747442
2025 Pleiotrophin (PTN) secreted by cardiac fibroblasts acts on SDC4 as a receptor on cardiac fibroblasts and macrophages, promoting fibroblast proliferation/invasion and macrophage inflammatory cytokine release (TNF-α, IL-6, Cox-2), contributing to pressure overload-induced hypertrophic cardiomyopathy. This was validated in vitro (ELISA, RT-qPCR, EdU staining, Transwell) and in vivo (TAC mouse model, western blot, immunofluorescence). scRNA-seq CellChat analysis, RT-qPCR, ELISA, EdU staining, Transwell assay, western blot, immunofluorescence, TAC mouse model Life sciences Medium 39765325
2025 Fibrotic lung ECM enhances fibroblast activation via SDC4-regulated integrin-αvβ1 expression and activation, and FAK/AKT phosphorylation. Duolink-proximity ligation assay confirmed extracellular interaction between SDC4 and integrin-αvβ1. SDC4 knockdown inhibited fibrotic ECM-induced TGF-β1 synthesis and PKCα activation. An interfering peptide (SDC4^87-131) disrupted SDC4-integrin-αvβ1 interaction, suppressing FAK/AKT, Smad2/3, and PKCα/NF-κB pathways. Decellularized lung ECM model, siRNA knockdown, Duolink-proximity ligation assay, western blotting, anti-SDC4 blocking antibody, peptide interference, AlphaFold2-Multimer docking Regenerative biomaterials Medium 40747330
2026 SDC4 silencing in anoikis-resistant endothelial cells arrested the cell cycle at the restriction point (G1/S) by increasing p27 expression (impairing cyclin E-CDK2 activity) and reducing cyclin B1, and increased susceptibility to anoikis. SDC4 thus modulates cell cycle regulatory machinery to support proliferation in anoikis-resistant tumor cells. miRNA-mediated SDC4 silencing, qPCR, western blotting, flow cytometry, cell viability assay after adhesion blockade Cytotechnology Medium 41890271
2026 SDC4 is a direct interactor of IP6K1; IP6K1 colocalizes and co-migrates with pepsinogen C (PGC) granules in AGS cells in an SDC4-dependent manner. CRISPR/Cas9 deletion of IP6K1 in AGS cells reduced PGC granule formation, which was restored by reintroduction of catalytically active or inactive IP6K1, indicating the scaffolding role of IP6K1 involves SDC4 for secretory granule biogenesis. CRISPR/Cas9 KO, Co-IP (IP6K1 identified SDC4 as interactor), co-localization/co-migration imaging, rescue by IP6K1 reintroduction (catalytic vs. inactive mutant) American journal of physiology. Gastrointestinal and liver physiology Medium 42053465
2026 TNF activates the TNFR1-TRADD/TRAF2/RIPK1-MAPK-SDC4 signaling axis, leading SDC4 to activate RhoA/ROCK signaling, which promotes cytoskeletal reorganization and actin bundle formation at the interface between SARS-CoV-2-infected cells and adjacent cells, blocking syncytia formation and viral cell-to-cell spreading. Pathway dissection (genetic/pharmacological perturbation of TNFR1, TRADD, TRAF2, RIPK1, MAPK, SDC4, RhoA/ROCK), actin imaging, syncytia quantification Cell insight Medium 41783041
2026 MALL (MAL-like protein) binds to SDC4 and promotes its recycling to the plasma membrane, increasing surface SDC4 abundance. This MALL-SDC4 axis promotes RhoA/p-MLC2-dependent amoeboid motility in pancreatic cancer cells and sensitizes them to Schwann cell-derived pleiotrophin for directed neural invasion. Disruption of MALL or SDC4 in cancer cells, or AAV-mediated SDC4 knockdown in KPC mice, significantly reduced perineural invasion and tumor burden. Co-IP (MALL-SDC4 interaction), surface SDC4 quantification after MALL perturbation, RhoA/p-MLC2 pathway assay, genetic perturbation (siRNA/CRISPR), AAV-mediated knockdown in KPC mice, in vivo PNI and tumor burden assessment Advanced science Medium 42017444
2026 IL1β stimulates esophageal cancer cell proliferation via NF-κB-dependent upregulation of SDC4. NF-κB directly binds the SDC4 promoter (confirmed by ChIP), and SDC4 knockdown suppressed IL1β-driven proliferation, whereas overexpression enhanced it. EGCG blocked the IL1β-NF-κB-SDC4 axis by inhibiting NF-κB nuclear translocation. ChIP assay, siRNA knockdown, overexpression, proliferation assays, NF-κB inhibition by EGCG Cellular signalling Medium 41534677
2025 KLK8 (kallikrein-related peptidase 8) cleaves SDC4, contributing to loss of glycocalyx integrity in glomerular endothelial cells in diabetic nephropathy. Endothelial Klk8 knockout mice showed improved SDC4 expression in glomeruli and reduced diabetic nephropathy hallmarks. Circulatory levels of KLK8 and soluble SDC4 were positively correlated in diabetic nephropathy patients. Global and endothelial-specific Klk8 KO mice (STZ model), proteomics, scRNA-seq, biochemical cleavage assays, correlation analysis in DN patients bioRxiv (preprint)preprint Low
2025 SDC4 expressed on the surface of HEK293F-derived miniEVs (extracellular vesicles) confers anti-inflammatory properties. Engineered overexpression of SDC4 increased heparan sulfate on EV surfaces and produced potent anti-inflammatory effects in vitro and in a murine peritonitis model. Heparinase treatment slightly reduced the anti-inflammatory effect, suggesting HS chains partly mediate this activity. EV engineering (SDC4 overexpression), quantitative proteomics, heparinase treatment, in vitro inflammatory assays, in vivo peritonitis model bioRxiv (preprint)preprint Low

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Molecular cloning of amphiglycan, a novel integral membrane heparan sulfate proteoglycan expressed by epithelial and fibroblastic cells. The Journal of cell biology 154 1500433
1996 Human ryudocan from endothelium-like cells binds basic fibroblast growth factor, midkine, and tissue factor pathway inhibitor. The Journal of biological chemistry 109 8621465
1994 Characterization of ryudocan glycosaminoglycan acceptor sites. The Journal of biological chemistry 69 7520439
2021 Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma. Cell death & disease 50 33990545
2021 LncRNA WDFY3-AS2 promotes cisplatin resistance and the cancer stem cell in ovarian cancer by regulating hsa-miR-139-5p/SDC4 axis. Cancer cell international 43 34051810
2013 Up-regulation of TGM2 with ITGB1 and SDC4 is important in the development and metastasis of renal cell carcinoma. Urologic oncology 42 23499501
2018 SDC4 Gene Silencing Favors Human Papillary Thyroid Carcinoma Cell Apoptosis and Inhibits Epithelial Mesenchymal Transition via Wnt/β-Catenin Pathway. Molecules and cells 41 30165731
2001 Plasma levels of syndecan-4 (ryudocan) are elevated in patients with acute myocardial infarction. Thrombosis and haemostasis 39 11372670
1993 Human ryudocan core protein: molecular cloning and characterization of the cDNA, and chromosomal localization of the gene. Biochemical and biophysical research communications 27 7916598
1997 Molecular cloning, genomic organization, promoter activity, and tissue-specific expression of the mouse ryudocan gene. Journal of biochemistry 24 9276666
2017 Dioscin Inhibits HSC-T6 Cell Migration via Adjusting SDC-4 Expression: Insights from iTRAQ-Based Quantitative Proteomics. Frontiers in pharmacology 23 29033837
2021 Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer. Molecular carcinogenesis 20 33721368
1996 Structural organization and promoter activity of the human ryudocan gene. Journal of biochemistry 18 8797100
2024 Oleic Acid Inhibits SDC4 and Promotes Ferroptosis in Lung Cancer Through GPX4/ACSL4. The clinical respiratory journal 17 39400975
2015 Metabolism and successful aging: Polymorphic variation of syndecan-4 (SDC4) gene associate with longevity and lipid profile in healthy elderly Italian subjects. Mechanisms of ageing and development 17 26254886
2023 Low expression of ZFP36L1 in osteosarcoma promotes lung metastasis by inhibiting the SDC4-TGF-β signaling feedback loop. Oncogene 15 37935976
2025 COL1A1-positive endothelial cells promote gastric cancer progression via the ANGPTL4-SDC4 axis driven by endothelial-to-mesenchymal transition. Cancer letters 14 40254092
2019 TNF-α Regulates ITGβ1 and SYND4 Expression in Nucleus Pulposus Cells: Activation of FAK/PI3K Signaling. Inflammation 14 31111299
2014 Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 25361632
1993 Isolation and characterization of ryudocan and syndecan heparan sulfate proteoglycans, core proteins, and cDNAs from a rat endothelial cell line. Haemostasis 11 8495865
2022 Eltrombopag binds SDC4 directly and enhances MAPK signaling and macropinocytosis in cancer cells. American journal of cancer research 10 35812066
2022 Circ_0058063 promotes progression of thyroid cancer by sponging miR-330-3p/SDC4 axis. Anti-cancer drugs 9 35324533
2000 Ryudocan expression by luteinized granulosa cells is associated with the process of follicle atresia. Fertility and sterility 9 11119752
2024 Sdc4 deletion perturbs intervertebral disc matrix homeostasis and promotes early osteopenia in the aging mouse spine. Matrix biology : journal of the International Society for Matrix Biology 8 38806135
2022 ADK-VR2, a cell line derived from a treatment-naïve patient with SDC4-ROS1 fusion-positive primarily crizotinib-resistant NSCLC: a novel preclinical model for new drug development of ROS1-rearranged NSCLC. Translational lung cancer research 6 36519016
2025 PTN secreted by cardiac fibroblasts promotes myocardial fibrosis and inflammation of pressure overload-induced hypertrophic cardiomyopathy through the PTN-SDC4 pathway. Life sciences 5 39765325
2022 LINC00707 Promotes Cell Proliferation in Cervical Cancer via the miR-374c-5p/SDC4 Axis. BioMed research international 5 35937409
2000 Molecular biology of ryudocan, an endothelial heparan sulfate proteoglycan. Seminars in thrombosis and hemostasis 5 10805285
2025 Unraveling the Role of MDK-SDC4 Interaction in Pancreatic Cancer-Associated New-Onset Diabetes by Single-Cell Transcriptomic Analysis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 40709672
2026 Cholesterol-metabolic tumor-associated macrophages regulate tumor budding-like cell subpopulation to promote chordoma stemness via BACH1/ANGPTL4/SDC4 axis. Neuro-oncology 3 41390963
2025 SDC4 identified as an oncogenic target gene of NF-κB in TNFα-Induced tumor cells. Scientific reports 3 40341546
2025 Fibrotic lung ECM upregulates SDC4/integrin-αvβ1 interaction and the interfering peptide SDC487-131 and its derivative peptides alleviate pulmonary fibrosis. Regenerative biomaterials 3 40747330
2023 Different effects of crizotinib treatment in two non-small cell lung cancer patients with SDC4::ROS1 fusion variants. Thoracic cancer 3 38093515
2022 SDC4-rs1981429 and ATM-rs228590 may provide early biomarkers of breast cancer risk. Journal of cancer research and clinical oncology 3 36152082
2025 Endothelial HOXB9/SDC4 signaling exacerbates post-ischemic blood-brain and blood-spinal cord barrier disruption by promoting PKCα activation. Brain research bulletin 2 40571266
2025 SDC4 drives fibrotic remodeling of the intervertebral disc under altered spinal loading. Cell death & disease 2 41053113
2021 Case Report: Detection of Double ROS1 Translocations, SDC4-ROS1 and ROS1-GK, in a Lung Adenocarcinoma Patient and Response to Crizotinib. Frontiers in medicine 2 34616749
2019 Corrigendum: Dioscin Inhibits HSC-T6 Cell Migration via Adjusting SDC-4 Expression: Insights From iTRAQ-Based Quantitative Proteomics. Frontiers in pharmacology 2 31579122
1995 Molecular cloning of the human ryudocan promoter. Biochemical and biophysical research communications 2 7626103
2025 SDC4 drives fibrotic remodeling of the intervertebral disc under altered spinal loading. bioRxiv : the preprint server for biology 1 40161806
2026 The IL1β-NFκB-SDC4 signaling Axis promotes esophageal cancer cell proliferation and is suppressed by EGCG. Cellular signalling 0 41534677
2026 SDC4 is a novel target of the KLF5 transcription factor. Biochemical and biophysical research communications 0 41747442
2026 TNF inhibits SARS-CoV-2 induced cell-cell fusion through activating the SDC4-RhoA signaling to promote actin bundles formation. Cell insight 0 41783041
2026 SDC4 silencing promotes cell cycle arrest at the restriction point (R point) in anoikis-resistant endothelial cells. Cytotechnology 0 41890271
2026 Formation of the pre-metastatic niche by COL9A1 + cancer-associated fibroblasts via SDC4 engagement promotes multi-organ metastasis in gastric cancer. Journal of gastroenterology 0 41999506
2026 Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42017444
2026 IP6K1 interacts with the syndecan SDC4 to support secretory granule biogenesis in gastric chief cells. American journal of physiology. Gastrointestinal and liver physiology 0 42053465
2026 Erratum to "TNF inhibits SARS-CoV-2 induced cell-cell fusion through activating the SDC4-RhoA signaling to promote actin bundles formation" [Cell Insight 5 (2026) 100310]. Cell insight 0 42205795
2025 Visceral crisis in a patient with non-small cell lung cancer and ROS1::SDC4 fusion: intrinsic resistance to entrectinib via L2026M mutation-a case report. Translational lung cancer research 0 40535089
2025 Unveiling the Role of Sdc4+ Monocytes in NASH: A Single-Cell RNA Sequencing Study. Immunological investigations 0 40768295
2025 Macrophage-derived FN1 promotes peritoneal cavity metastasis of gastric cancer by inhibiting the Hippo signaling pathway via SDC4. Biochimica et biophysica acta. Molecular cell research 0 41005547
2025 Identification of SDC4 as a potential target for obesity via integrated analysis of the lncRNA-miRNA-mRNA network in visceral adipose tissue. Adipocyte 0 41199597
2025 Effect of the sdc4 gene knockdown on muscle development in zebrafish. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 0 41390996
2024 Retracted: LINC00707 Promotes Cell Proliferation in Cervical Cancer via the miR-374c-5p/SDC4 Axis. BioMed research international 0 38549976

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