Affinage

SDC1

Syndecan-1 · UniProt P18827

Round 2 corrected
Length
310 aa
Mass
32.5 kDa
Annotated
2026-04-28
130 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Syndecan-1 (SDC1/CD138) is a transmembrane heparan sulfate proteoglycan that integrates extracellular ligand binding, integrin activation, receptor tyrosine kinase co-signaling, and intracellular membrane trafficking to regulate cell adhesion, migration, exosome biogenesis, and autophagy. Its heparan sulfate chains bind growth factors (FGF-2, HGF, VEGF), chemokines (CXCL1, CCL5), and viral glycoproteins (HIV gp120, HSV-1), functioning as a coreceptor that concentrates ligands at the cell surface and, after ectodomain shedding by MT1-MMP at Gly245–Leu246, presents them in trans within the extracellular matrix to coordinate neutrophil chemotaxis and angiogenesis (PMID:12464176, PMID:12904296, PMID:20097882). The SDC1 core-protein ectodomain directly activates αvβ3 and αvβ5 integrins and captures IGF1R to suppress ASK1-mediated apoptosis, while its cytoplasmic domain drives syntenin-1/ALIX-dependent exosome biogenesis and mediates ligand internalization through a non-clathrin pathway (PMID:15479743, PMID:27364558, PMID:22660413, PMID:9294130). Following irradiation, SDC1 forms a complex with TGM2, FLOT1, and BHMT that transports TGM2 to lysosomes and coordinates autophagosome–lysosome fusion, conferring radioresistance (PMID:35913916, PMID:37441590).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1989 High

    Establishing that SDC1 exhibits stage-specific expression during B-cell differentiation — present on precursor B cells, lost upon circulation, and re-expressed on plasma cells — linked its function to matrix-adhesion-dependent developmental transitions.

    Evidence Immunofluorescence, flow cytometry, and in situ hybridization on bone marrow sections and sorted B-cell populations

    PMID:2519615

    Open questions at the time
    • Transcriptional and epigenetic regulators of stage-specific SDC1 expression were not identified
    • Functional consequence of re-expression on plasma cells was not tested
  2. 1994 High

    Demonstrating that SDC1 expression inhibits invasion through sulfated HS chains established SDC1 as an anti-invasive factor and identified the glycosaminoglycan moiety as the functional determinant.

    Evidence Stable SDC1 cDNA transfection in B-lymphoid cells, collagen gel invasion assay with heparin competition and chlorate treatment

    PMID:8051085

    Open questions at the time
    • The specific HS-binding ECM ligand(s) mediating invasion suppression were not identified
    • Whether the core protein contributes independently was not tested
  3. 1997 High

    Identifying that SDC1's transmembrane and cytoplasmic domains drive ligand internalization via a non-clathrin, actin- and tyrosine-kinase-dependent pathway revealed a cell-autonomous endocytic function for syndecans beyond passive ligand display.

    Evidence Chimeric FcR-SDC1 constructs in CHO cells, lipoprotein degradation assays, pharmacological inhibition (cytochalasin B, genistein)

    PMID:9294130

    Open questions at the time
    • The specific cytoplasmic domain motifs required for internalization were not mapped
    • Adaptor proteins linking the cytoplasmic tail to the actin-dependent machinery were not identified
  4. 2000 High

    Showing that SDC1 (and SDC4) mediate bacterial invasion via HS chains and intracellular domains demonstrated that pathogens exploit the syndecan endocytic machinery for cellular entry.

    Evidence Overexpression and dominant-negative SDC1/SDC4 constructs in HeLa cells, Neisseria gonorrhoeae invasion assays

    PMID:11207564

    Open questions at the time
    • Whether the SDC1 cytoplasmic domain motifs required for invasion overlap with those for constitutive endocytosis was untested
    • Downstream signaling from SDC1 during bacterial uptake was not characterized
  5. 2002 High

    Demonstrating that MMP-7-shed SDC1 ectodomain binds CXCL1 and is required for neutrophil transepithelial migration in vivo resolved how a proteoglycan shedding event creates a chemokine gradient for innate immune cell recruitment.

    Evidence MMP-7-null and SDC1-null mice, bronchoalveolar lavage, co-IP of KC with shed SDC1

    PMID:12464176

    Open questions at the time
    • Whether other shed syndecans can compensate in vivo was not tested
    • Structural basis of CXCL1–HS interaction specificity was not resolved
  6. 2002 High

    Identifying SDC1 as an HGF coreceptor that enhances Met activation via its HS chains established SDC1 as a growth-factor co-receptor in myeloma, linking it to PI3K/Akt and RAS/MAPK survival signaling.

    Evidence HGF binding assays, Met phosphorylation, HS-blocking controls, myeloma cell proliferation assays

    PMID:11830493

    Open questions at the time
    • HS fine structure requirements for HGF binding were not defined
    • Whether shed SDC1 retains coreceptor function for HGF/Met was not examined
  7. 2003 High

    Mapping the MT1-MMP cleavage site to Gly245–Leu246 and showing TIMP-2 (but not TIMP-1) inhibition defined the enzymatic mechanism and specificity of SDC1 ectodomain shedding.

    Evidence Recombinant MMP cleavage assay, site-directed mutagenesis at Gly245, TIMP inhibition, migration assays

    PMID:12904296 PMID:23384311

    Open questions at the time
    • In vivo contribution of MT1-MMP versus other sheddases (MMP-7, ADAM family) was not quantified
    • Regulation of MT1-MMP access to the SDC1 juxtamembrane region in tissue context was unclear
  8. 2004 High

    Establishing that the SDC1 core-protein ectodomain directly activates αvβ3 integrin for vitronectin-dependent spreading and migration revealed that SDC1 functions as an integrin co-activator independent of its HS chains.

    Evidence GPI-anchored ectodomain, recombinant protein competition, anti-ectodomain antibodies, siRNA, cell spreading assays

    PMID:15479743

    Open questions at the time
    • The precise ectodomain region contacting αvβ3 had not been mapped to residue-level resolution
    • Whether this interaction is direct or requires an intermediary was not definitively resolved
  9. 2009 High

    Extending the integrin co-activation mechanism to αvβ5 and developing the synstatin (SSTN) inhibitory peptide demonstrated that the SDC1–integrin axis drives angiogenesis and tumor growth in vivo, validating it as a therapeutic target.

    Evidence Deletion mutants, integrin activation assays, aortic explant angiogenesis, SSTN peptide, orthotopic mammary tumor model

    PMID:19255147

    Open questions at the time
    • Structural basis of the SSTN-targeted interface was not resolved
    • Potential off-target effects of SSTN on other syndecans were not fully excluded
  10. 2010 High

    Showing that shed SDC1 captures VEGF via HS and simultaneously activates integrins via its core protein to promote endothelial invasion unified the shedding and integrin-activation functions into a single pro-angiogenic mechanism in the myeloma microenvironment.

    Evidence VEGF capture assays, endothelial invasion, synstatin inhibition, heparanase high/low myeloma cells

    PMID:20097882

    Open questions at the time
    • Quantitative stoichiometry of the ternary SDC1–VEGF–integrin complex was not established
    • Whether this mechanism operates outside hematological malignancies was not tested
  11. 2012 High

    Discovering that SDC1 controls exosome biogenesis through its cytoplasmic domain–syntenin-1–ALIX interaction defined a novel trafficking role for syndecans in intraluminal endosomal budding and ESCRT-dependent exosome formation.

    Evidence Co-IP, syntenin/ALIX interaction mapping, heparan sulfate depletion, intraluminal budding assays, FGF signaling readouts

    PMID:22660413

    Open questions at the time
    • Which cytoplasmic domain residues are essential for syntenin-1 binding was not precisely defined for SDC1
    • Cargo selectivity mechanism beyond CD63 was not resolved
  12. 2012 High

    Demonstrating that cis-attached HS chains suppress MMP-mediated shedding of the SDC1 ectodomain established an autoregulatory mechanism whereby HS modification status gates shedding efficiency.

    Evidence Enzymatic HS removal, HS-deficient SDC1 constructs, MMP shedding assays across cell types

    PMID:22298773

    Open questions at the time
    • Structural basis of HS-mediated steric shielding was not resolved
    • How heparanase coordinates this gate in physiological contexts was only partly addressed
  13. 2015 High

    Showing that heparanase stimulates the SDC1–syntenin–ALIX exosome pathway by trimming HS chains connected the HS autoregulatory gate to exosome cargo loading and secretion.

    Evidence Heparanase gain/loss-of-function, exosomal secretion, syntenin/ALIX epistasis

    PMID:25732677

    Open questions at the time
    • Whether heparanase activity is regulated at the endosome or only at the cell surface was not resolved
    • Cargo selection beyond CD63 and syntenin was not examined
  14. 2016 High

    Identifying that SDC1 captures IGF1R and that IGF1R kinase phosphorylates and inhibits ASK1, with disruption by synstatin-IGF1R triggering apoptosis, revealed a survival signaling axis in myeloma that operates through the SDC1 ectodomain.

    Evidence Co-IP, kinase assays, synstatin-IGF1R peptide, phospho-specific antibodies, JNK/caspase-3 apoptosis assays, xenograft model

    PMID:27364558

    Open questions at the time
    • Whether other receptor tyrosine kinases are similarly captured by SDC1 was not systematically tested
    • Crystal structure of the SDC1–IGF1R interface is lacking
  15. 2019 High

    Demonstrating that dynamic CD138 surface cycling regulates a proliferation-versus-dissemination switch in myeloma — with CD138-high cells proliferating and CD138-negative cells migrating — linked SDC1 endocytic recycling to tumor dissemination in vivo.

    Evidence Vk*MYC myeloma model, intravital imaging, CD138 neutralization, endocytic trafficking assays

    PMID:31439945

    Open questions at the time
    • The endocytic machinery regulating SDC1 recycling rate was not fully identified
    • Whether this switch operates in other SDC1-expressing cancers was not tested
  16. 2022 High

    Discovering that irradiation induces a SDC1–TGM2–FLOT1 complex that transports TGM2 to lysosomes to coordinate autophagosome–lysosome fusion via LC3 recognition revealed a previously unknown role for SDC1 in autophagy and radioresistance.

    Evidence TMT proteomics, co-IP, mRFP-GFP-LC3 flux assay, TEM, xenograft model

    PMID:35913916

    Open questions at the time
    • Whether this autophagy role is specific to radiation stress or operates under basal conditions was not determined
    • The SDC1 domain mediating TGM2 interaction was not mapped
  17. 2023 High

    Extending the autophagy complex to include BHMT as a fourth component recognized by TGM2 on autophagosomes completed the model of SDC1-mediated autophagosome–lysosome tethering in GBM radioresistance.

    Evidence Co-IP of quaternary complex, colony formation, mRFP-GFP-LC3, TEM, immunofluorescence

    PMID:37441590

    Open questions at the time
    • Structural basis of the quaternary complex remains unresolved
    • Whether this pathway operates in non-GBM cell types is unknown
    • The signal triggering SDC1–TGM2 complex formation after irradiation is not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SDC1's integrin co-activation, exosome biogenesis, and autophagy functions are coordinated — whether they represent independent parallel pathways or are interconnected through SDC1 trafficking — remains an open question.
  • No study has examined cross-talk between SDC1 exosome and autophagy pathways
  • Structural models of the SDC1 ectodomain bound to integrins or IGF1R are lacking
  • Cell-type-specific hierarchy of SDC1 functions has not been systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098631 cell adhesion mediator activity 4 GO:0098772 molecular function regulator activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 3 GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0031012 extracellular matrix 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
FLOT1IGF1RITGAVITGB3MMP14PDCD6IPSDCBPTGM2
Complex memberships
SDC1–TGM2–FLOT1–BHMTSDC1–syntenin-1–ALIX

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Syndecan-1 (SDC1) controls exosome biogenesis through its cytoplasmic domain interaction with syntenin-1, which in turn binds ALIX via LYPX(n)L motifs, supporting intraluminal budding of endosomal membranes. Exosome formation depends on heparan sulfate availability, syndecans, ALIX, and ESCRTs, and impacts FGF signal trafficking. Co-immunoprecipitation, syntenin/ALIX interaction mapping, heparan sulfate depletion, intraluminal budding assays, FGF signaling readouts Nature cell biology High 22660413
2015 Heparanase, the only mammalian enzyme that cleaves heparan sulfate internally, stimulates the syndecan-syntenin-ALIX exosome pathway by trimming heparan sulfate chains on SDC1, fostering intraluminal budding and selective cargo (CD63, syntenin-1, syndecan) loading into exosomes in a syntenin- and ALIX-dependent manner. Exosomal secretion assays, heparanase gain/loss-of-function, endosomal budding imaging, syntenin/ALIX epistasis experiments Cell research High 25732677
2002 Matrilysin (MMP-7) sheds syndecan-1 ectodomains from the epithelial surface; shed syndecan-1 binds the CXC chemokine KC (CXCL1), and this complex directs neutrophil transepithelial migration into the alveolar space during acute lung injury. In syndecan-1 null mice, KC is absent from lavage fluid, demonstrating SDC1 is required for chemokine presentation. Matrilysin null mice, syndecan-1 null mice, bronchoalveolar lavage analysis, in vitro MMP cleavage assay, co-immunoprecipitation of KC with shed syndecan-1 Cell High 12464176
2003 MT1-MMP cleaves the syndecan-1 core protein preferentially at the Gly245-Leu246 peptide bond, shedding the ectodomain. This shedding stimulates cell migration; substitution of Gly245 with Leu significantly reduces shedding and migration. MT3-MMP also cleaves syndecan-1; TIMP-2 (but not TIMP-1) blocks MT1-MMP-mediated shedding. Expression cloning, co-expression in HEK293T, recombinant MMP cleavage assay, site-directed mutagenesis, TIMP inhibition, migration assays on collagen The Journal of biological chemistry High 12904296
2013 Matrix metalloproteinases (MMP) cleave syndecan-1 and syndecan-4 ectodomains at two membrane-proximal regions (6 and 15 residues from the transmembrane domain) and at sites 35–40 residues C-terminal from heparan sulfate substitution sites. MT1-MMP cleavage sites in syndecan-1 were confirmed by site-directed mutagenesis. Recombinant MMP cleavage, peptide mapping, site-directed mutagenesis The FEBS journal High 23384311
2012 The heparan sulfate chains attached to the syndecan-1 core protein suppress ectodomain shedding by matrix metalloproteinases. Enzymatic removal or genetic absence of heparan sulfate dramatically enhances MMP-mediated shedding; exogenous heparan sulfate does not inhibit shedding, indicating cis-attachment to the core protein is required. Enhanced shedding also triggers compensatory upregulation of core protein synthesis. Enzymatic HS degradation (heparanase, heparitinase), HS-deficient syndecan-1 constructs, MMP shedding assays, multiple cell types and species The Journal of biological chemistry High 22298773
1994 Expression of syndecan-1 inhibits invasion of human B lymphoid cells into type I collagen gels. Transfection of syndecan-1 cDNA into non-expressing ARH-77 cells drastically reduces their invasion capacity. Inhibition is reversed by pre-incubating collagen with heparin or by treating cells with chlorate (inhibitor of glycosaminoglycan sulfation), demonstrating that sulfated HS chains on SDC1 mediate the anti-invasive function. Stable cDNA transfection, collagen gel invasion assay, heparin competition, chlorate treatment The Journal of biological chemistry High 8051085
2004 The syndecan-1 ectodomain couples syndecan-1 to the αvβ3 integrin, which depends on the SDC1 ectodomain to become activated and mediate cell spreading on vitronectin. Competition with recombinant SDC1 ectodomain protein, anti-ectodomain antibodies, ectodomain mutations, or siRNA knockdown of SDC1 all disrupt αvβ3-dependent spreading and migration. GPI-anchored ectodomain expression, recombinant protein competition, anti-ectodomain antibodies, mutagenesis, siRNA knockdown, cell spreading assays The Journal of cell biology High 15479743
2009 Syndecan-1 (Sdc1) regulates αvβ3 and αvβ5 integrin activation during angiogenesis. The SDC1 core protein ectodomain associates with these integrins, and a derived peptide inhibitor synstatin (SSTN) blocks this coupling, inhibiting integrin activation, angiogenesis in vitro, and tumor growth in vivo in mouse models. SDC1 deletion mutants, integrin activation assays, aortic explant angiogenesis model, SSTN peptide inhibitor, orthotopic mammary tumor model The Journal of experimental medicine High 19255147
2016 Syndecan-1 captures IGF1 receptor (IGF1R) constitutively and in a ligand-stimulated manner. IGF1R kinase activity in both fractions is suppressed by synstatin-IGF1R (SSTN), a peptide that disrupts IGF1R capture by SDC1. Sdc1-captured IGF1R phosphorylates ASK1 at Tyr and Ser83/Ser966, inhibiting ASK1. When IGF1R–Sdc1 coupling is blocked, ASK1 activates JNK- and caspase-3-mediated apoptosis in multiple myeloma cells. Co-immunoprecipitation, kinase activity assays, synstatin peptide inhibitor, phospho-specific antibodies, apoptosis assays (JNK, caspase-3), xenograft tumor model Cancer research High 27364558
2002 Syndecan-1 binds hepatocyte growth factor (HGF) via its heparan sulfate chains and functions as a coreceptor that strongly promotes HGF-mediated Met receptor tyrosine kinase activation in multiple myeloma cells, enhancing downstream PI3K/Akt and RAS/MAPK signaling and myeloma cell survival and proliferation. HGF binding assays, heparan sulfate blocking, Met phosphorylation assays, PI3K/Akt and MAPK pathway readouts, myeloma cell proliferation/survival assays Blood High 11830493
1997 Syndecan-1 core protein transmembrane and cytoplasmic domains directly mediate ligand internalization via a pathway distinct from clathrin-coated pits (t1/2 ~1 h, sensitive to cytochalasin B and genistein). Transfection of syndecan-1 into CHO cells increases lipoprotein uptake and degradation; a chimeric FcR-Synd1 construct confirms the transmembrane/cytoplasmic domain alone triggers internalization upon ligand clustering. Transfection of syndecan core protein cDNAs in CHO cells, chimeric receptor constructs, lipoprotein degradation assays, pharmacological inhibition (cytochalasin B, genistein), kinetics comparison with coated-pit pathway The Journal of clinical investigation High 9294130
2009 Sdc1-null primary keratinocytes show constitutively elevated TGFβ1 signaling (elevated phospho-Smad2, dual-reporter assay), increased surface expression of αvβ6, αvβ8, and α6β4 integrins, slower migration, and impaired collagen matrix deposition. Migration rates are restored by fibronectin/collagen I or laminin-332 substrates, by αv or α6 integrin-blocking antibodies, or by TGFβ1 treatment, placing Sdc1 as a regulator of integrin surface expression and TGFβ1 signaling in keratinocytes. Primary Sdc1-null mouse keratinocytes, migration assays, integrin surface expression by flow cytometry, Smad2 phosphorylation, dual-reporter TGFβ1 assay, function-blocking antibodies Journal of cell science High 17666434
2009 In squamous cell carcinoma cells, SDC1 (Sdc1) functions as a collagen I co-adhesion receptor alongside α2β1 integrin. siRNA depletion of Sdc1 reduces adhesion to collagen I and ablates adhesion-induced RhoA activation while strongly activating Rac1, leading to reduced focal adhesion formation but enhanced cell spreading and motility specifically on collagen I substrates. siRNA knockdown, adhesion assays, small GTPase pull-down (RhoA, Rac1), focal adhesion imaging, motility assays on multiple ECM substrates Experimental cell research High 20036233
2010 Heparanase-enhanced shedding of syndecan-1 from myeloma cells promotes angiogenesis: the heparan sulfate chains of shed syndecan-1 capture VEGF and anchor the SDC1/VEGF complex to extracellular matrix, where the complex simultaneously activates integrin (via the SDC1 core protein) and VEGF receptors on endothelial cells. Synstatin peptide blocking the integrin-activating region of the SDC1 core protein inhibits endothelial invasion. Conditioned medium assays, VEGF capture assays, heparan sulfate binding experiments, endothelial invasion assays, synstatin inhibitor, heparanase high/low expressing myeloma cells Blood High 20097882
2000 Syndecan-1 and syndecan-4 mediate invasion of OpaHSPG-expressing Neisseria gonorrhoeae into epithelial cells via their heparan sulfate chains. The intracellular domains of both syndecans are required for uptake; dominant-negative constructs lacking the intracellular domain abrogate invasion. Syndecan-4 mutants defective in the PKC/PIP2 binding dimerization motif or the C-terminal EFYA motif (syntenin/CASK binding) also lose invasion-mediating capacity. Overexpression and dominant-negative transfection in HeLa cells, syndecan-1 and -4 mutant constructs, invasion assays Cellular microbiology High 11207564
2003 Syndecan functions as an in trans HIV receptor in non-permissive cells: the heparan sulfate chains of syndecan bind HIV gp120, enabling virus adsorption. Syndecan preserves virus infectivity for up to one week (vs. <1 day for unbound virus) and enhances in trans infectivity of primary lentiviruses. The syndecan-rich endothelial lining of the vasculature can provide a microenvironment that boosts HIV replication in T cells. HIV adsorption assays in non-permissive syndecan-expressing cells, viral infectivity assays, gp120-HS binding, time-course infectivity preservation assays Immunity High 12530973
2009 Both membrane-bound and soluble (shed) forms of syndecan-1 have distinct roles in breast cancer: overexpression of WT Sdc1 increases cell proliferation and inhibits invasion; constitutively shed Sdc1 decreases proliferation and promotes invasion into Matrigel via a pathway involving downregulation of TIMP-1 and E-cadherin. FGF-2-mediated MAPK signaling is reduced by siRNA-mediated Sdc1 knockdown. Stable transfection of WT, constitutively shed, and uncleavable Sdc1 constructs, Matrigel invasion, siRNA, Affymetrix microarray, MMP inhibitors, Western blotting Carcinogenesis High 19126645
2022 SDC1 forms a complex with TGM2 (transglutaminase 2) after irradiation and transports it from the cell membrane to lysosomes via flotillin-1 (FLOT1). At lysosomes, TGM2 binds LC3 via two LIR motifs, coordinating autophagosome-lysosome encounter; lysosomal EPG5 then recognizes LC3 and stabilizes the STX17-SNAP29-VAMP8 SNARE complex for fusion. SDC1 or TGM2 knockdown inhibits autophagosome-lysosome fusion and enhances radiosensitivity of GBM cells. TMT quantitative proteomics, siRNA knockdown, co-IP, mRFP-GFP-LC3 autophagy flux assay, immunofluorescence, transmission electron microscopy, xenograft model Autophagy High 35913916
2023 SDC1 forms a quaternary complex with TGM2, FLOT1, and BHMT that maintains autophagic flux in irradiated GBM cells: SDC1 transports TGM2 to lysosomes via FLOT1 binding, and TGM2 then recognizes BHMT on autophagosomes to coordinate autophagosome-lysosome fusion, enhancing radioresistance. Co-IP, co-immunoprecipitation of four-component complex, colony formation, flow cytometry, qPCR, Western blot, mRFP-GFP-LC3, transmission electron microscopy, immunofluorescence Theranostics High 37441590
2003 RANTES (CCL5) binds specifically to syndecan-1 and syndecan-4 (but not syndecan-2) on human monocyte-derived macrophages via glycosaminoglycan chains, as shown by co-immunoprecipitation. Glycosaminidase pre-treatment strongly decreases RANTES binding to both syndecans and to CCR5, suggesting that SDC1/SDC4 GAG-mediated RANTES binding facilitates subsequent interaction with CCR5. Co-immunoprecipitation on primary human macrophages, glycosaminidase pre-treatment, competitive binding assays Biochimica et biophysica acta Medium 14637022
2014 Syndecan-1 (Sdc-1) expression is associated with differentiated M2 macrophages with high intrinsic motility. Sdc-1-deficient macrophages show impaired migration and enhanced adhesion in vitro. In a thioglycollate peritonitis model in Sdc-1(-/-) mice, inflammatory cell infiltration is normal but lymphatic clearance of macrophages is significantly delayed, and ApoE(-/-)Sdc-1(-/-) mice show enhanced atherosclerosis. Sdc-1 null mouse model, macrophage migration and adhesion assays, peritonitis model, ApoE/Sdc-1 double-knockout atherosclerosis model Arteriosclerosis, thrombosis, and vascular biology Medium 25550207
2006 Anthrax hemolytic virulence factors (AnlB sphingomyelinase, AnlO pore-forming factor, anthrax lethal toxin) accelerate SDC1 ectodomain shedding from epithelial cells by activating cellular sheddase through Syk-family cytoplasmic tyrosine kinases. LT and AnlO modulate ERK1/2 and p38 MAPK pathways during this process. Accelerated SDC1 shedding also occurs in vivo in mice challenged with B. anthracis spores. Shedding assays with recombinant bacterial virulence factors, kinase inhibitor experiments, ERK/p38/JNK pathway analysis, in vivo mouse anthrax model, circulating ectodomain measurement BMC microbiology Medium 16464252
2009 Syndecan-1 knockdown by siRNA in urothelial carcinoma cells downregulates transcription factor JunB and the long isoform of FLIP (FLIP-L), leading to caspase-dependent apoptosis. In an orthotopic mouse bladder cancer model, intravesical siRNA-mediated SDC1 silencing reduces tumor growth. siRNA knockdown, qRT-PCR, Western blot, pan-caspase inhibitor rescue, orthotopic mouse bladder tumor model Cancer science Medium 19860843
2017 SDC1 silencing in triple-negative inflammatory breast cancer cells reduces ALDH1 activity and CD44+/CD24- cancer stem cell subset, decreases IL-6, IL-8, CCL20, gp130, and EGFR mRNA, and suppresses STAT3, NFκB, Notch-1/-2, and Notch-3/-4 protein levels. Gamma-secretase inhibition experiments indicate SDC1 regulates IL-6, IL-8, EGFR, and p-Akt via Notch signaling. siRNA knockdown, flow cytometry, Western blotting, secretome profiling, pharmacological Notch inhibition (gamma-secretase inhibitor), qPCR, 3D spheroid/colony assays Molecular cancer Medium 28270211
2013 Sdc1 overexpression in infarcted rat myocardium inhibits the p38 MAPK signaling pathway, reduces post-MI inflammatory cell infiltration and cardiomyocyte apoptosis, decreases collagen synthesis, and improves ventricular remodeling and cardiac function. Adenoviral Sdc1 overexpression in rat MI model, p38 MAPK pathway analysis, histology, cardiac function measurements, apoptosis assays Inflammation Medium 23264165
2015 Syndecan-1 overexpression in malignant mesothelioma cells downregulates SULF1 (a 6-O-sulfate-removing enzyme), alters the heparan sulfate biosynthetic machinery to produce a 2.7-fold reduction in HS content but increased overall sulfation with 2.5-fold more trisulfated disaccharides, and activates ERK1/2 6-fold while inhibiting Akt, WNK1, and c-Jun, resulting in G1 cell cycle arrest. SDC1 overexpression, HS biochemical characterization, SULF1/2 expression analysis, ERK/Akt/WNK1/c-Jun pathway assays, cell cycle analysis, pleural effusion samples Cellular signalling Medium 26210886
2021 EZH2 promotes histone H3K27 methylation at the miR-138 promoter in chondrocytes to suppress miR-138 expression, which in turn relieves repression of its target gene SDC1, increasing SDC1 protein levels. Elevated SDC1 promotes expression of cartilage catabolism-related factors (MMP-13, ADAMTS-4, ADAMTS-5) and cartilage degeneration in an OA model. EZH2 depletion rescues the phenotype. ChIP-qPCR for EZH2/H3K27me3 at miR-138 promoter, luciferase reporter for miR-138/SDC1 targeting, IL-1β OA cell model, OA mouse model, flow cytometry for apoptosis, Western blot Laboratory investigation Medium 33692439
1989 Syndecan (SDC1) is expressed on precursor B cells in bone marrow, lost immediately before B lymphocyte release into circulation, absent on circulating B lymphocytes, and re-expressed upon B cell differentiation into plasma cells in interstitial matrices — demonstrating stage-specific expression linked to matrix adhesion during B cell differentiation. Immunofluorescence on bone marrow sections and sorted cell populations, flow cytometry, in situ hybridization Cell regulation High 2519615
2019 Dynamic SDC1 (CD138) surface expression regulates a switch between proliferative and disseminating states in multiple myeloma: CD138-high cells are more proliferative and less motile, while CD138-negative cells are more motile and disseminate readily. Neutralizing CD138 rapidly triggers myeloma cell migration in vivo and intravasation. SDC1 surface expression is dynamically recycled through endocytic trafficking in response to serum levels. In vivo Vk*MYC myeloma model, intravital imaging, CD138 neutralization, in vitro migration assays, endocytic trafficking assays, flow cytometry, bortezomib combination treatment Leukemia High 31439945
2010 HSV-1 infection increases syndecan-1 and syndecan-2 protein synthesis and cell surface HS expression; siRNA-mediated gene silencing of syndecan-1 (and syndecan-2) reduces HSV-1 entry, plaque formation, and facilitates cell survival, indicating syndecan-1 core protein plays an active role in HSV-1 infection beyond just providing HS attachment sites. siRNA knockdown, HSV-1 entry assays, plaque formation assays, cell viability assays, surface HS measurement The Journal of general virology Medium 21148276

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nature cell biology 1486 22660413
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2002 Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 615 12464176
2000 Internalization of HIV-1 tat requires cell surface heparan sulfate proteoglycans. The Journal of biological chemistry 613 11024024
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2011 A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Annals of surgery 456 21772125
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
1997 HIV-1 Tat protein exits from cells via a leaderless secretory pathway and binds to extracellular matrix-associated heparan sulfate proteoglycans through its basic region. AIDS (London, England) 374 9342064
1989 B lymphocytes express and lose syndecan at specific stages of differentiation. Cell regulation 344 2519615
1993 The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. Proceedings of the National Academy of Sciences of the United States of America 331 7690138
2003 Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration. The Journal of biological chemistry 320 12904296
1998 Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells. The Journal of cell biology 313 9660868
2011 Molecular functions of syndecan-1 in disease. Matrix biology : journal of the International Society for Matrix Biology 285 22033227
2015 Heparanase activates the syndecan-syntenin-ALIX exosome pathway. Cell research 270 25732677
2017 Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways. Molecular cancer 218 28270211
2009 Syndecan-1 regulates alphavbeta3 and alphavbeta5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. The Journal of experimental medicine 217 19255147
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