Affinage

GPC1

Glypican-1 · UniProt P35052

Length
558 aa
Mass
61.7 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 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

GPC1 (glypican-1) is a GPI-anchored, heparan-sulfate-bearing cell-surface proteoglycan that acts as a heparan-sulfate-dependent co-receptor and scaffold, concentrating and presenting secreted ligands and morphogens to amplify growth-factor and developmental signaling (PMID:11375980, PMID:35348113). Its heparan sulfate chains, particularly N-sulfated disaccharides, mediate high-affinity ligand binding—including Slit-2 and FGF2—and the glycanated proteoglycan binds substantially more avidly than the core protein alone (PMID:11375980, PMID:35348113); among heparan sulfate proteoglycan subclasses, GPC1 is the principal, rate-limiting driver of unconventional FGF2 secretion while being dispensable for FGF2 signaling into cells (PMID:35348113). At the cell surface GPC1 functions as a required co-receptor for angiogenesis, interacting directly with VEGFR2 and c-Met and acting cell-intrinsically and from the host vasculature to support VEGF-A-driven endothelial mitogenesis, tumor growth, and metastasis (PMID:18064304, PMID:34957110). In endothelial caveolae it serves as a mechanotransducer that is specifically required for shear-stress-induced eNOS activation and protects against substrate-stiffness-induced endothelial dysfunction (PMID:24480876, PMID:32647868). GPC1 modulates multiple morphogen pathways in a context-dependent manner: it is the principal alpha4(V)-collagen-binding proteoglycan on Schwann cells and is required for myelination (PMID:16407548), positively regulates Hedgehog signaling during biliary development (PMID:23336978), and physically binds BMP2 to inhibit BMP2/4/7 signaling and osteogenesis (PMID:23624389). In proliferating cells GPC1 drives G1/S progression and DNA replication by engaging the Skp2 autoinduction loop—suppressing CDK inhibitors and inducing Skp2, CDK2, and cyclin E—while activating ERK/MAPK, PI3K/Akt, Wnt, and BMP signaling (PMID:22203671, PMID:24019070). GPC1 also scaffolds the cellular prion protein in lipid rafts, mediating its raft association and copper-dependent internalization and facilitating PrPc-to-PrPSc conversion (PMID:19936054, PMID:16923158).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 Medium

    Establishing the biosynthetic and recycling logic of GPC1 was needed to understand how its heparan sulfate chains are assembled and regenerated, the basis for its ligand-binding function.

    Evidence Biochemical reconstitution of GPI-anchor attachment, HS chain assembly, and endoheparanase/NO-driven deaminative cleavage and reformation in vitro

    PMID:10963998

    Open questions at the time
    • Single-lab in vitro reconstitution with limited structural validation
    • Physiological relevance of the recycling pathway not tested in cells
  2. 2001 High

    Demonstrating high-affinity, sulfation-dependent binding of Slit-2 to GPC1 heparan sulfate chains established GPC1 as a ligand-binding co-receptor rather than an inert structural proteoglycan.

    Evidence ELISA binding with glypican-Fc, heparinase and desulfated-heparin competition, co-IP after co-transfection, and CNS immunolocalization

    PMID:11375980

    Open questions at the time
    • Functional consequence of GPC1-Slit-2 binding on axon guidance not tested
    • Does not establish whether GPC1 presents Slit-2 to a signaling receptor
  3. 2006 High

    Identifying GPC1 as the principal alpha4(V)-collagen-binding proteoglycan on Schwann cells linked it to ECM assembly and peripheral myelination.

    Evidence siRNA knockdown with adhesion, ECM incorporation, and Schwann cell–DRG co-culture myelination assays

    PMID:16407548

    Open questions at the time
    • Whether HS chains or core protein mediate alpha4(V) binding not resolved
    • No in vivo myelination phenotype
  4. 2006 Medium

    Defining a copper- and PrPc-dependent route for GPC1 internalization connected GPC1 trafficking to prion protein biology in lipid rafts.

    Evidence Confocal co-localization, immunomagnetic isolation, siRNA silencing, and a Cu-binding-domain-deletion PrPc construct

    PMID:16923158

    Open questions at the time
    • Single lab
    • Mechanism of nitrosylation-driven autoprocessing not biochemically resolved
  5. 2008 High

    Genetic and antisense loss-of-function across cancer and host compartments established GPC1 as both cell-intrinsic and stromal driver of tumor growth, angiogenesis, and metastasis.

    Evidence Antisense knockdown in PANC-1, xenografts in athymic and GPC1-null host mice, metastasis quantification, and VEGF-A mitogenesis on isolated endothelial cells

    PMID:18064304

    Open questions at the time
    • Direct ligand/receptor mechanism for the angiogenic defect not defined in this study
    • Does not identify the GPC1-dependent signaling axis
  6. 2009 High

    Showing GPC1 scaffolds both PrPc and PrPSc in rafts and is required for PrPSc formation gave GPC1 a mechanistic role in prion conversion.

    Evidence Reciprocal co-IP, detergent-resistant raft fractionation, confocal IF, and siRNA in scrapie-infected N2a cells

    PMID:19936054

    Open questions at the time
    • Whether GPC1 directly catalyzes or merely co-localizes the isoforms unresolved
    • No structural model of the scaffold
  7. 2011 Medium

    Linking GPC1 to the mitogen-independent Skp2 autoinduction loop explained how it inactivates the G1/S checkpoint to drive proliferation.

    Evidence GPC1 overexpression/RNAi, cell-cycle regulator immunoblotting, signaling reporter assays, and p21 RNAi epistasis in brain endothelial cells

    PMID:22203671

    Open questions at the time
    • Single lab
    • How surface GPC1 transmits signal to the Skp2 loop mechanistically unclear
  8. 2013 Medium

    Demonstrating that GPC1 drives S-phase entry, DNA rereplication, and damage via Skp2/CDK2/cyclin E extended its proliferative role to genomic instability in glioma and astrocytes.

    Evidence Bidirectional manipulation, BrdU/EdU incorporation, flow cytometry, and Skp2/CDK2/cyclin E knockdown epistasis with PI3K/ERK inhibitors

    PMID:24019070

    Open questions at the time
    • Single lab
    • Upstream receptor coupling to ERK/Akt not defined
  9. 2013 Medium

    Establishing GPC1 as a positive Hedgehog regulator in biliary development and a biliary atresia susceptibility gene linked GPC1 to a morphogen pathway in vivo.

    Evidence Zebrafish morpholino knockdown with cyclopamine rescue and Sonic Hedgehog injection phenocopy, plus copy-number analysis in patients

    PMID:23336978

    Open questions at the time
    • Single lab
    • Molecular mechanism of GPC1 Hh modulation not defined
  10. 2013 Medium

    Identifying direct GPC1-BMP2 binding and BMP inhibition showed GPC1 can negatively, not only positively, regulate morphogen signaling in a context-dependent manner.

    Evidence Recombinant-protein physical interaction, antibody blockade, overexpression, SMAD phosphorylation, and osteogenesis assays in cranial suture mesenchyme

    PMID:23624389

    Open questions at the time
    • Single lab
    • Whether HS chains or core protein mediate BMP2 binding not resolved
  11. 2014 Medium

    Pinpointing GPC1 (and not syndecan-1) as the specific mediator of shear-stress-induced eNOS activation defined a distinct mechanotransduction role in caveolae.

    Evidence siRNA of GPC1 vs SDC1, heparinase III, shear stress on EC monolayers, and eNOS activity and morphology readouts

    PMID:24480876

    Open questions at the time
    • Single lab
    • Physical coupling between GPC1 and eNOS not directly demonstrated
  12. 2021 High

    Systematic subclass comparison established GPC1 as the principal, rate-limiting heparan sulfate proteoglycan for unconventional FGF2 secretion while being dispensable for FGF2 signaling into cells.

    Evidence siRNA across HSPG subclasses, FGF2 secretion assay, HS structural analysis, and FGF2 binding/signaling assays

    PMID:35348113

    Open questions at the time
    • Mechanism by which GPC1 carries FGF2 across the membrane not resolved
    • Whether N-sulfated disaccharide enrichment is GPC1-specific in vivo untested
  13. 2021 Medium

    Showing GPC1 is required for VEGF/HGF-induced angiogenesis and interacts with VEGFR2 and c-Met provided the receptor-level basis for its pro-angiogenic function.

    Evidence siRNA knockdown, PLC cleavage, pseudotube formation, and GPC1-VEGFR2/c-Met interaction assays in HDMEC

    PMID:34957110

    Open questions at the time
    • Single lab
    • Whether interactions are HS-mediated and direct in vivo not established
  14. 2021 Medium

    Linking GPC1 expression to substrate stiffness and endothelial protection extended its mechanobiology beyond shear flow to matrix-stiffness sensing.

    Evidence Defined-stiffness substrates, bidirectional manipulation, GPC1-/- mice, and EC dysfunction readouts (inflammation, EndMT, NO)

    PMID:32647868

    Open questions at the time
    • Single lab
    • Signaling intermediates between GPC1 and EndMT not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GPI-anchored proteoglycan can act as both positive (FGF2, VEGF, Hedgehog, proliferation) and negative (BMP2) regulator across tissues—and what determines which receptor or ligand it couples to in a given context—remains unresolved.
  • No structural model of GPC1-receptor complexes
  • Determinants of context-specific positive vs negative regulation unknown
  • In vivo HS-chain dependence of most interactions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0038024 cargo receptor activity 2 GO:0060089 molecular transducer activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 3 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2
Partners
BMP2COL5A3FGF2METPRNPSLIT2VEGFR2
Complex memberships
caveolae

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 GPC1 (glypican-1) binds Slit-2 protein via its heparan sulfate chains with high affinity (Kd ~80-110 nM); the glycanated proteoglycan binds with ~10-fold higher affinity than the core protein alone; O-sulfate groups on heparan sulfate chains are critical for this interaction; co-immunoprecipitation confirmed the interaction in vivo after co-transfection of 293 cells, and colocalization was demonstrated immunocytochemically in the embryonic and adult CNS. ELISA binding assay with glypican-Fc fusion protein and recombinant Slit-2; co-immunoprecipitation after co-transfection; heparinase treatment and desulfated heparin competition; immunocytochemistry The Journal of biological chemistry High 11375980
2006 GPC1 is the principal alpha4(V) collagen-binding heparan sulfate proteoglycan on the Schwann cell surface. siRNA-mediated knockdown of GPC1 reduced binding of alpha4(V) collagen N-terminal domain to Schwann cells, decreased Schwann cell adhesion and spreading on alpha4(V)-NTD, impaired incorporation of alpha4(V) collagen into ECM, and significantly inhibited myelination in Schwann cell–DRG neuron co-cultures. siRNA knockdown; adhesion/spreading assays; ECM incorporation assay; Schwann cell–DRG neuron co-culture myelination assay The Journal of neuroscience High 16407548
2008 Both cancer cell-derived and host-derived GPC1 are required for efficient tumor growth, metastasis, and angiogenesis. Antisense-mediated GPC1 downregulation in PANC-1 cells prolonged doubling times, decreased anchorage-independent growth in vitro, and attenuated tumor growth, angiogenesis, and metastasis in athymic mice. GPC1-null host mice showed decreased tumor angiogenesis, metastasis, and fewer pulmonary metastases with multiple cancer cell lines; hepatic endothelial cells from GPC1-null mice had an attenuated mitogenic response to VEGF-A. Antisense knockdown; xenograft tumor implantation; GPC1 knockout mouse; in vitro proliferation and soft-agar assays; metastasis quantification; VEGF-A mitogenesis assay on isolated endothelial cells The Journal of clinical investigation High 18064304
2009 GPC1 mediates lipid raft association of the cellular prion protein (PrPc) and facilitates conversion to the disease isoform (PrPSc). Depletion of GPC1 (the major neuronal GPI-anchored HSPG) displaced PrPc from rafts and promoted its endocytosis. Both PrPc and PrPSc co-immunoprecipitated with GPC1. Critically, GPC1 siRNA knockdown in scrapie-infected N2a cells significantly reduced PrPSc formation. siRNA knockdown; co-immunoprecipitation; detergent-resistant raft fractionation; confocal immunofluorescence; scrapie-infected cell model PLoS pathogens High 19936054
2006 GPC1 controls copper-dependent co-internalization of PrPc from the cell surface to perinuclear compartments. PrPc provides the Cu2+ ions required to nitrosylate thiol groups in the GPC1 core protein, enabling GPC1 recycling via a caveolin-associated pathway and heparan sulfate autoprocessing. A PrPc construct lacking the copper-binding domain failed to drive GPC1 internalization and abrogated GPC1 autoprocessing. GPC1 silencing had no effect on copper-stimulated PrPc endocytosis. Confocal immunofluorescence; immunomagnetic isolation; siRNA silencing; copper treatment; dominant-negative PrPc construct lacking Cu-binding domain Journal of neurochemistry Medium 16923158
2011 GPC1 overexpression in brain endothelial cells inactivates the G1/S checkpoint by activating the mitogen-independent Skp2 autoinduction loop: GPC1 suppresses CDK inhibitors (p21, p27, p16, p19) and D cyclins, induces CDK2 and Skp2, and activates ERK/MAPK, Wnt, and BMP signaling pathways. p21 knockdown by RNAi phenocopied GPC1 effects on cell cycle regulators. GPC1 overexpression and RNAi knockdown; immunoblotting for cell cycle regulators; luciferase reporter assays for signaling pathways; flow cytometry for cell cycle phasing The Journal of biological chemistry Medium 22203671
2013 GPC1 expression strongly stimulates S phase entry, DNA replication, and causes DNA rereplication and damage in glioma cells and normal astrocytes; it downregulates pRb, Cip/Kip CKIs, and CDH1, upregulates cyclin E, CDK2, Skp2, and Cdt1, and constitutively activates ERK/MAPK and PI3K/Akt pathways. Knockdown of Skp2, CDK2, or cyclin E reduced S phase and aneuploid fractions, confirming their role downstream of GPC1. GPC1 overexpression and siRNA knockdown; BrdU/EdU incorporation; flow cytometry; immunoblotting; PI3K/Akt and ERK pathway inhibitors Molecular and cellular biology Medium 24019070
2013 GPC1 acts as a susceptibility gene for biliary atresia and regulates Hedgehog signaling in biliary development. Morpholino knockdown of gpc1 in zebrafish caused developmental biliary defects; partial rescue by a Hedgehog antagonist (cyclopamine) and induction of biliary defects by recombinant Sonic Hedgehog injection phenocopying the morphant established GPC1 as a positive regulator of Hh signaling in this context. Morpholino antisense knockdown in zebrafish; cyclopamine rescue; recombinant Sonic Hedgehog injection; biliary morphology analysis; copy number variant analysis in BA patients Gastroenterology Medium 23336978
2014 GPC1 mediates shear stress-induced eNOS activation in endothelial cells. RNA silencing of GPC1 (but not syndecan-1) blocked flow-induced eNOS activation, while SDC1 knockdown (but not GPC1) attenuated cell elongation and alignment. GPC1 is localized to caveolae where eNOS resides, consistent with its role as a centralized mechanotransmission agent. siRNA silencing of GPC1 or SDC1; heparinase III treatment; shear stress application to EC monolayers; eNOS activity measurement; cell morphology analysis Integrative biology Medium 24480876
2013 GPC1 and GPC3 physically interact with BMP2 and inhibit BMP2, BMP4, and BMP7 activities in cranial suture mesenchymal cells. Immunoblockade of endogenous GPC1 and GPC3 potentiated BMP2 activity; overexpression or addition of recombinant GPC1/GPC3 protein inhibited BMP2 signaling and BMP2-mediated osteogenesis. GPC1 and GPC3 inhibit both SMAD-dependent and SMAD-independent BMP2 signaling pathways. Recombinant protein binding (physical interaction assay); antibody blockade of endogenous glypicans; overexpression; SMAD phosphorylation immunoblotting; osteogenesis assay in primary suture mesenchymal cells Bone Medium 23624389
2021 GPC1 is the principal and rate-limiting factor that drives unconventional secretion of FGF2. Among all heparan sulfate proteoglycan subclasses (syndecans, perlecans, glypicans), only GPC1 knockdown substantially reduced FGF2 secretion. Disaccharides with N-linked sulfate groups are enriched in GPC1 heparan sulfate chains and mediate high-affinity FGF2 binding. GPC1 was dispensable for FGF2 signaling into cells. siRNA knockdown of specific HSPG subclasses; FGF2 secretion assay; heparan sulfate chain structural analysis; FGF2 binding affinity measurements; FGF2 signaling assay eLife High 35348113
2021 GPC1 is required for VEGF- and HGF-induced angiogenesis in human dermal microvascular endothelial cells (HDMEC). GPC1 siRNA transfection completely abrogated pseudotube formation induced by keratinocyte-conditioned media. Cleavage of GPC1 from the cell surface by phospholipase C promoted HDMEC proliferation. GPC1 was shown to interact directly with VEGFR2 and c-Met to regulate angiogenesis. siRNA knockdown; phospholipase C cleavage; pseudotube formation assay; co-immunoprecipitation/direct interaction assay for GPC1-VEGFR2 and GPC1-c-Met Frontiers in cell and developmental biology Medium 34957110
2021 GPC1 protects endothelial cells from stiffness-mediated dysfunction. On stiff substrates (10 kPa), GPC1 gene and protein expression were reduced; GPC1 siRNA silencing on soft substrates recapitulated stiffness-induced EC dysfunction (inflammation, proliferation, EndMT); GPC1 overexpression reversed these effects. GPC1 knockout mice (GPC1-/-) showed exacerbated endothelial dysfunction in young but not old mice (where GPC1 is already low). Polyacrylamide gel substrates of defined stiffness; siRNA silencing and plasmid overexpression; GPC1 knockout mouse model; monocyte adhesion assay; NO measurement; gene expression analysis Cardiovascular research Medium 32647868
2022 GPC1 promotes colorectal cancer cell growth and migration through the TGF-β1/SMAD2 signaling pathway. GPC1 knockdown in CRC cell lines inhibited proliferation, migration, and promoted apoptosis; it suppressed TGF-β1 levels and p-SMAD2 while increasing total SMAD2, placing GPC1 upstream of TGF-β1/SMAD2 signaling in CRC. siRNA knockdown; CCK-8 proliferation assay; Transwell migration assay; apoptosis assay; western blotting for TGF-β1, SMAD2, and p-SMAD2 PloS one Low 35671267
2006 GPC1 downregulation in pancreatic cancer cells reduces anchorage-independent growth and slightly modifies TGF-β1, activin-A, and BMP-2 signaling (growth, p21 induction, Smad2 phosphorylation). GPC1 mRNA correlates with activin and BMP receptor expression in pancreatic tissues. Stable antisense transfection of GPC1; MTT and soft agar growth assays; immunoblotting for p-Smad1, p-Smad2, p21; quantitative RT-PCR for receptors International journal of oncology Low 17016645
2000 GPC1 (glypican) biosynthesis involves GPI-anchor attachment and heparan sulfate chain assembly on serine residues in consensus sequences. Chain-truncated GPC1 formed by endoheparanase cleavage at GlcNH2 residues followed by NO-derived nitrite deaminative cleavage can serve as a precursor for reformation of full-length proteoglycan, establishing a recycling pathway for GPC1 heparan sulfate chains. Biochemical characterization; in vitro enzymatic assays; GlcNH2 identification; NO/nitrite deaminative cleavage assay Matrix biology Medium 10963998
2019 GPC1 overexpression in colon cancer cells activates epithelial-mesenchymal transition (EMT), increasing invasion and migration; GPC1 silencing inactivated EMT and decreased invasion and migration. miR-96-5p and miR-149 were shown to regulate GPC1 expression, and their overexpression decreased GPC1 levels, GPC1+ exosome secretion, and tumor growth. GPC1 overexpression and siRNA knockdown; EMT marker immunoblotting; invasion/migration Transwell assays; adenoviral miRNA overexpression; xenograft tumor model Oncotarget Low 29254156

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2242 26106858
2017 Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Medicinal research reviews 311 28621802
2010 Glypican-3: a new target for cancer immunotherapy. European journal of cancer (Oxford, England : 1990) 185 21112773
2014 Shear-induced endothelial NOS activation and remodeling via heparan sulfate, glypican-1, and syndecan-1. Integrative biology : quantitative biosciences from nano to macro 177 24480876
2001 Glypican-3 expression is silenced in human breast cancer. Oncogene 172 11704870
2006 Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas. Human pathology 167 16949914
2008 Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells. The Journal of clinical investigation 151 18064304
2017 GPC1 exosome and its regulatory miRNAs are specific markers for the detection and target therapy of colorectal cancer. Journal of cellular and molecular medicine 149 28233416
2001 Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis. Developmental biology 146 11180950
2006 Glypican 3: a novel marker in testicular germ cell tumors. The American journal of surgical pathology 144 17122513
2018 Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden. Oncotarget 122 29721179
2020 Glypican-3: A New Target for Diagnosis and Treatment of Hepatocellular Carcinoma. Journal of Cancer 121 32127929
1997 Expression of the cell surface proteoglycan glypican-5 is developmentally regulated in kidney, limb, and brain. Developmental biology 118 9331333
2022 Glypican-3: A Novel and Promising Target for the Treatment of Hepatocellular Carcinoma. Frontiers in oncology 116 35251989
2019 Glypican-3-Specific Antibody Drug Conjugates Targeting Hepatocellular Carcinoma. Hepatology (Baltimore, Md.) 111 30353932
2019 Glypican 3-Targeted Therapy in Hepatocellular Carcinoma. Cancers 107 31510063
1999 Glypican-6, a new member of the glypican family of cell surface heparan sulfate proteoglycans. The Journal of biological chemistry 107 10480909
2001 Characterization of Slit protein interactions with glypican-1. The Journal of biological chemistry 104 11375980
2019 Next-Generation Cancer Immunotherapy Targeting Glypican-3. Frontiers in oncology 103 31024850
2013 Evidence from human and zebrafish that GPC1 is a biliary atresia susceptibility gene. Gastroenterology 102 23336978
2008 Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development. Histology and histopathology 102 18785116
2009 Glypican-3 expression in clear cell adenocarcinoma of the ovary. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 94 19329941
2019 The Role of Glypican-3 in Regulating Wnt, YAP, and Hedgehog in Liver Cancer. Frontiers in oncology 93 31428581
2008 Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 84 18469798
2007 Role for amplification and expression of glypican-5 in rhabdomyosarcoma. Cancer research 83 17210683
2001 Glypican-3 expression in Wilms tumor and hepatoblastoma. Journal of pediatric hematology/oncology 81 11878776
2014 Regulation of Zn and Fe transporters by the GPC1 gene during early wheat monocarpic senescence. BMC plant biology 75 25524236
2009 Glypican-1 mediates both prion protein lipid raft association and disease isoform formation. PLoS pathogens 71 19936054
2006 Oncofetal protein glypican-3 in testicular germ-cell tumor. Virchows Archiv : an international journal of pathology 68 16896894
2009 Glypican-3: a novel diagnostic marker for hepatocellular carcinoma and more. Advances in anatomic pathology 67 19550373
2000 Dally-like protein, a new Drosophila glypican with expression overlapping with wingless. Mechanisms of development 64 11091094
2021 Role of glypican-1 in regulating multiple cellular signaling pathways. American journal of physiology. Cell physiology 63 34550795
1996 The glypican family of heparan sulfate proteoglycans: major cell-surface proteoglycans of the developing nervous system. Perspectives on developmental neurobiology 61 9117265
2008 Expression of glypican 3 in ovarian and extragonadal germ cell tumors. American journal of clinical pathology 58 18628091
2022 Astrocyte-secreted glypican-4 drives APOE4-dependent tau hyperphosphorylation. Proceedings of the National Academy of Sciences of the United States of America 57 35969759
2019 The Expression, Regulation, and Biomarker Potential of Glypican-1 in Cancer. Frontiers in oncology 57 31355137
2021 The glycocalyx core protein Glypican 1 protects vessel wall endothelial cells from stiffness-mediated dysfunction and disease. Cardiovascular research 56 32647868
2007 Glypican-3 expression in primary and recurrent ovarian carcinomas. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 56 17581422
2020 GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab. eLife 54 32228854
2023 The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer. Nature communications 52 37031249
2019 Combined Exosomal GPC1, CD82, and Serum CA19-9 as Multiplex Targets: A Specific, Sensitive, and Reproducible Detection Panel for the Diagnosis of Pancreatic Cancer. Molecular cancer research : MCR 52 31662449
2017 The clinical significance of circulating GPC1 positive exosomes and its regulative miRNAs in colon cancer patients. Oncotarget 52 29254156
2017 Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer. International journal of cancer 51 29055044
1996 Developmental and FGF-2-mediated regulation of syndecans (1-4) and glypican in oligodendrocytes. Molecular and cellular neurosciences 51 8793863
2006 Glypican-1 and alpha4(V) collagen are required for Schwann cell myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 16407548
2014 GPC1 regulated by miR-96-5p, rather than miR-182-5p, in inhibition of pancreatic carcinoma cell proliferation. International journal of molecular sciences 49 24736782
2019 Glypican-1 and glycoprotein 2 bearing extracellular vesicles do not discern pancreatic cancer from benign pancreatic diseases. Oncotarget 48 30800217
2017 Significance of Glypican-3 (GPC3) Expression in Hepatocellular Cancer Diagnosis. Medical science monitor : international medical journal of experimental and clinical research 48 28207681
2018 Cancer immunotherapy-targeted glypican-3 or neoantigens. Cancer science 47 29285841
2013 Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3. Bone 47 23624389
2015 Glypican-3 is a biomarker and a therapeutic target of hepatocellular carcinoma. Hepatobiliary & pancreatic diseases international : HBPD INT 44 26256079
2000 Biosynthesis of decorin and glypican. Matrix biology : journal of the International Society for Matrix Biology 43 10963998
2024 Peptide Binder to Glypican-3 as a Theranostic Agent for Hepatocellular Carcinoma. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 42 38423788
2012 Glypican-3 expression and its relationship with recurrence of HCC after liver transplantation. World journal of gastroenterology 41 22654434
2006 Correlation of glypican-1 expression with TGF-beta, BMP, and activin receptors in pancreatic ductal adenocarcinoma. International journal of oncology 39 17016645
2012 Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms. Human pathology 38 23079207
2014 Glypican 3 expression in pediatric malignant solid tumors. European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie 37 25344940
2024 The role of glypican-3 in hepatocellular carcinoma: Insights into diagnosis and therapeutic potential. European journal of medical research 36 39369212
1999 Expression pattern alterations of syndecans and glypican-1 in normal and pathological trophoblast. The Journal of pathology 35 10629564
2017 Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review). Oncology reports 34 28098909
2020 Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer. British journal of cancer 33 32152502
2017 New tumor suppressor microRNAs target glypican-3 in human liver cancer. Oncotarget 33 28476031
2020 The Role of Glypican-1 in the Tumour Microenvironment. Advances in experimental medicine and biology 32 32266658
2023 Structural and Functional Impact of Posttranslational Modification of Glypican-3 on Liver Carcinogenesis. Cancer research 30 37027004
2017 Imaging the expression of glypican-3 in hepatocellular carcinoma by PET. Amino acids 30 29204748
2014 Expression of glypican 3 enriches hepatocellular carcinoma development-related genes and associates with carcinogenesis in cirrhotic livers. Carcinogenesis 29 25542894
2006 Copper-dependent co-internalization of the prion protein and glypican-1. Journal of neurochemistry 29 16923158
2017 EVI1 modulates oncogenic role of GPC1 in pancreatic carcinogenesis. Oncotarget 28 29245923
2023 Glypican-3 knockdown inhibits the cell growth, stemness, and glycolysis development of hepatocellular carcinoma cells under hypoxic microenvironment through lactylation. Archives of physiology and biochemistry 27 37131292
2018 Detection of glypican-1 (GPC-1) expression in urine cell sediments in prostate cancer. PloS one 26 29672570
2014 Glypican 3 overexpression in primary and metastatic Wilms tumors. Virchows Archiv : an international journal of pathology 26 25366870
2018 The glycerophosphocholine acyltransferase Gpc1 is part of a phosphatidylcholine (PC)-remodeling pathway that alters PC species in yeast. The Journal of biological chemistry 25 30514764
2011 Expression and clinicopathologic significance of glypican 3 in hepatocellular carcinoma. Annals of diagnostic pathology 24 21371925
1999 Expression of glypican-4 in haematopoietic-progenitor and bone-marrow-stromal cells. The Biochemical journal 24 10585884
2016 Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer. Toxins 23 27669301
2020 Downregulation of glypican-4 facilitates breast cancer progression by inducing cell migration and proliferation. Biochemical and biophysical research communications 22 32199612
2022 Glypican-1 drives unconventional secretion of fibroblast growth factor 2. eLife 21 35348113
2022 GPC1 promotes the growth and migration of colorectal cancer cells through regulating the TGF-β1/SMAD2 signaling pathway. PloS one 21 35671267
2021 A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma. Neoplasia (New York, N.Y.) 21 34332450
2017 Can glypican-3 be a disease-specific biomarker? Clinical and translational medicine 21 28510121
2014 Glypican-3 as an emerging molecular target for hepatocellular carcinoma gene therapy. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 24633918
2022 The role of the glypican and syndecan families of heparan sulfate proteoglycans in cardiovascular function and disease. American journal of physiology. Cell physiology 20 35993518
2019 Glypican 6 is a putative biomarker for metastatic progression of cutaneous melanoma. PloS one 20 31199813
2010 Dual roles of Drosophila glypican Dally-like in Wingless/Wnt signaling and distribution. Methods in enzymology 20 20816203
2021 The Glypican-1/HGF/C-Met and Glypican-1/VEGF/VEGFR2 Ternary Complexes Regulate Hair Follicle Angiogenesis. Frontiers in cell and developmental biology 19 34957110
2021 Anti-Glypican-1 Antibody-drug Conjugate as Potential Therapy Against Tumor Cells and Tumor Vasculature for Glypican-1-Positive Cholangiocarcinoma. Molecular cancer therapeutics 18 34224365
2020 Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility. Aging 18 32315284
2020 Evaluation of Glypican-3 Expression in Hepatocellular Carcinoma by Using IDEAL IQ Magnetic Resonance Imaging. Academic radiology 18 32540197
2019 Paradoxical Role of Glypican-1 in Prostate Cancer Cell and Tumor Growth. Scientific reports 18 31391540
2019 Decreased expression of GPC1 in human skin keratinocytes and epidermis during ageing. Experimental gerontology 18 31430521
2014 Discovery and diagnostic value of a novel oncofetal protein: glypican 3. Advances in anatomic pathology 18 25299314
2013 Glypican 1 stimulates S phase entry and DNA replication in human glioma cells and normal astrocytes. Molecular and cellular biology 18 24019070
2011 Glypican-1 facilitates prion conversion in lipid rafts. Journal of neurochemistry 18 20681952
2011 Glypican-1 stimulates Skp2 autoinduction loop and G1/S transition in endothelial cells. The Journal of biological chemistry 18 22203671
2021 Glypican 4 mediates Wnt transport between germ layers via signaling filopodia. The Journal of cell biology 17 34591076
2022 Frequently expressed glypican-3 as a promising novel therapeutic target for osteosarcomas. Cancer science 16 35946078
2021 Advances in immunotherapeutic targets for childhood cancers: A focus on glypican-2 and B7-H3. Pharmacology & therapeutics 16 33992682
2009 Frequent expression of glypican-3 in Merkel cell carcinoma: an immunohistochemical study of 55 cases. Applied immunohistochemistry & molecular morphology : AIMM 16 18813128
2022 Hedgehog pathway modulation by glypican 3-conjugated heparan sulfate. Journal of cell science 15 35142364
2016 Common genetic variants of GPC1 gene reduce risk of biliary atresia in a Chinese population. Journal of pediatric surgery 15 27373597

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