Affinage

GPC3

Glypican-3 · UniProt P51654

Length
580 aa
Mass
65.6 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPC3 is a GPI-anchored cell-surface heparan sulfate proteoglycan that regulates cell growth, survival, and guidance by physically engaging multiple ligands and receptors at the plasma membrane (PMID:8589713, PMID:9628896, PMID:23624389). Through its core protein it directly binds and inhibits BMP2/4/7 signaling in a manner independent of GPI anchoring and glycanation, acting through both SMAD-dependent and SMAD-independent pathways (PMID:23624389), while its heparan sulfate chains bind FGF-2 (PMID:9065409) and LRP1; binding of Hedgehog to GPC3 competes with Patched and triggers LRP1-dependent endocytosis and degradation of the GPC3-Hh complex, attenuating Hedgehog signaling (PMID:22467855). Structurally, GPC3 assembles into a defined octameric complex with the guidance receptor Unc5D via glycan-glycan contacts between its N-linked glycans and C-mannosylated tryptophans of Unc5D, and this complex directs migration of cortical pyramidal neurons and cancer cells (PMID:36240740). GPC3 also induces GPI-anchor-dependent, glycosaminoglycan-independent apoptosis in a cell-type-specific manner, an effect reversible by IGF-2 (PMID:9628896), and it can suppress proliferation through G1 arrest (PMID:25168166) or by acting upstream of YAP in the Hippo pathway (PMID:23060277). Its promoter is recurrently silenced by CpG methylation across ovarian cancer, mesothelioma, and lung carcinoma, where re-expression suppresses colony formation and tumor growth, consistent with a context-dependent tumor-suppressor role (PMID:10029067, PMID:10656689, PMID:12816733). A conserved missense mutation (W296R) yields a poorly processed protein that fails to reach the cell surface, defining a loss-of-function mechanism (PMID:10814714).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 Medium

    Established GPC3 as a cell-surface heparan sulfate proteoglycan and provided the first candidate ligand by detecting a complex with IGF2, framing GPC3 as a modulator of growth-factor action.

    Evidence Western and ligand-blotting of glypican-3

    PMID:8589713

    Open questions at the time
    • IGF2 interaction was later contested by an ortholog study
    • no functional consequence of the complex demonstrated
  2. 1997 Medium

    Reassigned the ligand specificity by showing the rat ortholog does not bind IGF-2 but instead binds FGF-2 through its heparan sulfate chains, distinguishing core-protein from glycan-mediated interactions.

    Evidence Transfection, binding assay, heparin/heparitinase competition in two cell lines

    PMID:9065409

    Open questions at the time
    • functional outcome of FGF-2 binding not established
    • species/ortholog difference vs human GPC3 not resolved
  3. 1997 Medium

    Linked GPC3 transcription to cell shape and cytoskeletal state, indicating context-dependent regulation of its expression.

    Evidence Nuclear run-on, in situ hybridization, cytoskeletal disruption and culture-geometry perturbations in IEC-18 cells

    PMID:9281346

    Open questions at the time
    • transcription factors mediating shape-dependent induction unidentified
    • relevance to in vivo growth control unknown
  4. 1998 High

    Defined GPC3 as a cell-type-specific inducer of apoptosis and dissected the structural requirements, showing GPI anchoring is required while glycosaminoglycan chains are dispensable, and that IGF-2 can rescue.

    Evidence Ectopic expression with GPI-anchor and GAG-deficient mutants, apoptosis assays, IGF-2 rescue across multiple cell lines

    PMID:9628896

    Open questions at the time
    • molecular death pathway downstream of GPI-anchored GPC3 not identified
    • basis of cell-type specificity unexplained
  5. 1999 Medium

    Identified promoter hypermethylation as the silencing mechanism for GPC3 in cancer and X-inactivation, and showed re-expression suppresses colony formation, establishing a tumor-suppressor candidacy.

    Evidence Southern blot methylation analysis, in vitro reporter methylation, demethylating agent treatment, colony assays in ovarian cancer

    PMID:10029067 PMID:9892682

    Open questions at the time
    • growth-suppressive mechanism downstream of re-expression not defined
    • single-lab functional readout
  6. 2000 Medium

    Generalized epigenetic silencing to mesothelioma and characterized a loss-of-function missense mutation, connecting GPC3 inactivation to defective protein processing and surface localization.

    Evidence Methylation/demethylation and colony assays in mesothelioma; mutational and processing/heparan-sulfate surface-expression assays for W296R

    PMID:10656689 PMID:10814714

    Open questions at the time
    • whether W296R recapitulates disease phenotype in vivo not tested
    • tumor-suppressor mechanism still uncharacterized
  7. 2001 Medium

    Localized GPC3 protein to the differentiated syncytiotrophoblast and showed its induction during trophoblast differentiation, anchoring its role in a defined developmental tissue context.

    Evidence In situ hybridization, immunohistochemistry, RT-PCR in primary and cell-line trophoblasts

    PMID:11193214

    Open questions at the time
    • functional role in placental development not tested
    • signaling partners in syncytiotrophoblast unknown
  8. 2003 Medium

    Extended the epigenetic-silencing/tumor-suppressor model to lung carcinoma with in vivo evidence, showing re-expression sensitizes to etoposide-induced apoptosis and inhibits xenograft growth.

    Evidence Demethylation, ectopic expression, etoposide apoptosis assay, nude mouse xenograft

    PMID:12816733

    Open questions at the time
    • molecular basis of apoptosis sensitization not defined
    • in vivo data from single model
  9. 2012 High

    Resolved a mechanism for GPC3 control of Hedgehog signaling, showing GPC3 competes with Patched for Hh and that Hh binding triggers LRP1-dependent endocytosis and degradation of the GPC3-Hh complex via its heparan sulfate chains.

    Evidence Reciprocal co-immunoprecipitation, competition binding, lipid raft fractionation, endocytosis assays

    PMID:22467855

    Open questions at the time
    • in vivo relevance to Hedgehog-driven development/disease not addressed
    • fate of internalized Hh signaling output not quantified
  10. 2013 High

    Demonstrated direct core-protein-mediated inhibition of BMP signaling, separating this ligand-trap function from membrane anchoring and glycanation and linking it to control of osteogenesis.

    Evidence Co-IP of GPC3-BMP2, recombinant protein, immunoblockade, GPI/glycanation-deficient constructs, SMAD and osteogenesis assays

    PMID:23624389

    Open questions at the time
    • structural basis of BMP-core protein interaction not defined
    • in vivo skeletal phenotype not tested in this study
  11. 2013 Medium

    Placed GPC3 upstream of YAP in the Hippo pathway in hepatocellular carcinoma and reaffirmed growth-factor antagonism, where knockdown induces apoptosis rescued by YAP-1, and overexpression-induced apoptosis is blunted by IGF2/FGF2.

    Evidence siRNA knockdown, recombinant YAP-1 rescue, ectopic expression with IGF2/FGF2 rescue, apoptosis and proliferation/invasion assays in HCC lines

    PMID:23060277 PMID:23338845

    Open questions at the time
    • direction of GPC3 effect in HCC (pro- vs anti-tumor) varies by context
    • mechanism linking GPC3 to YAP regulation unresolved
  12. 2014 Medium

    Showed GPC3 can restrain proliferation independently of apoptosis via G1-phase cell cycle arrest in renal carcinoma, broadening its growth-suppressive repertoire.

    Evidence Overexpression, MTT, colony formation, cell-cycle and apoptosis flow cytometry in 786-O and ACHN cells

    PMID:25168166

    Open questions at the time
    • cell-cycle regulators mediating G1 arrest not identified
    • context-dependence relative to apoptotic effect unexplained
  13. 2022 High

    Provided the structural basis for GPC3 as a guidance co-receptor by solving the GPC3-Unc5D octameric complex assembled through glycan-glycan interactions, and validated its role in neuronal and cancer cell migration.

    Evidence X-ray crystallography, MD simulations, mass spectrometry, structure-based mutants, nanobodies, mouse cortex and xenograft migration assays

    PMID:36240740

    Open questions at the time
    • signaling output downstream of the GPC3-Unc5D complex not defined
    • how this guidance function integrates with GPC3's ligand-trap roles unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GPC3's distinct activities — apoptosis induction, BMP/FGF/Hh modulation, YAP regulation, and Unc5D-mediated guidance — are coordinated within a single cell and which dominate in specific developmental and tumor contexts remains unresolved.
  • no unified model reconciling tumor-suppressor vs tumor-promoting roles
  • downstream effectors of GPI-anchor-dependent apoptosis unknown
  • physiological significance of Furin cleavage and sEV-associated fragments not functionally established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-1266738 Developmental Biology 1 R-HSA-5357801 Programmed Cell Death 1
Partners
BMP2FGF2IGF2LRP1UNC5DYAP1
Complex memberships
GPC3-Hedgehog-LRP1 complexGPC3-Unc5D octameric complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 GPC3 encodes a cell-surface heparan sulfate proteoglycan (glypican-3) that forms a complex with insulin-like growth factor 2 (IGF2), as shown by western- and ligand-blotting experiments, suggesting it modulates IGF2 action in growth control. Western blotting and ligand-blotting Nature genetics Medium 8589713
1997 Rat GPC3 ortholog OCI-5 does NOT interact with IGF-2 (negative result); instead, OCI-5 binds FGF-2 via its heparan sulfate chains, as shown by transfection into two cell lines and inhibition by heparin or heparitinase. Transfection, co-immunoprecipitation/binding assay, heparin and heparitinase competition The Journal of biological chemistry Medium 9065409
1997 OCI-5/GPC3 mRNA expression in intestinal epithelial cells (IEC-18) is regulated by cell shape: rounded cell morphology (confluence, low calcium, spheroid culture) increases OCI-5 transcription, while cytoskeletal disruption with colchicine (causing cell flattening) abolishes induction. Nuclear run-on analysis confirmed transcriptional regulation. RNA in situ hybridization, nuclear run-on transcription assay, cytoskeletal disruption (colchicine, vanadate), low-calcium and spheroid culture conditions Experimental cell research Medium 9281346
1998 OCI-5/GPC3 induces apoptosis in mesothelioma (II14) and breast cancer (MCF-7) cell lines but not in NIH 3T3 fibroblasts or HT-29 cells (cell-line-specific effect). Membrane anchoring via GPI is required for apoptosis induction, but glycosaminoglycan chains are not. MCF-7 cells can be rescued from GPC3-induced apoptosis by IGF-2. Transfection and ectopic expression, GPI anchor mutants, glycosaminoglycan-deficient mutants, apoptosis assay, IGF-2 rescue experiment The Journal of cell biology High 9628896
1999 GPC3 promoter hypermethylation silences GPC3 expression in ovarian cancer cell lines; treatment with 5-aza-2'-deoxycytidine (demethylating agent) restores expression, and ectopic GPC3 expression inhibits colony formation, consistent with a tumor-suppressor role. Southern blot analysis of promoter methylation, demethylating agent treatment, colony-forming assay with ectopic GPC3 expression Cancer research Medium 10029067
1999 GPC3 promoter methylation on the inactive X allele mediates transcriptional repression via X inactivation; in vitro methylation of the GPC3 promoter in reporter constructs directly represses transcription. In vitro methylation of reporter constructs, Southern blot analysis of allele-specific methylation, azadeoxycytidine treatment Proceedings of the National Academy of Sciences of the United States of America Medium 9892682
2000 GPC3 is silenced in malignant mesothelioma predominantly through aberrant promoter methylation (not allelic loss or mutation); demethylation with 5-aza-2'-deoxycytidine restores GPC3 expression in MM cell lines, and ectopic GPC3 expression inhibits in vitro colony formation of MM cells. Northern blot, allelic loss analysis, mutational analysis, promoter methylation analysis, demethylating agent treatment, ectopic expression + colony formation assay Oncogene Medium 10656689
2000 A GPC3 missense mutation (W296R), which changes an amino acid conserved across all glypicans, results in a poorly processed protein that fails to increase cell surface expression of heparan sulfate, establishing it as a loss-of-function mutation affecting GPC3 processing and cell-surface localization. Mutational analysis, protein processing assay, heparan sulfate cell surface expression assay Human molecular genetics Medium 10814714
2003 GPC3 expression is epigenetically silenced by promoter hypermethylation in non-small cell lung carcinoma lines; ectopic GPC3 expression increases apoptosis response to etoposide and inhibits growth in nude mice, supporting a tumor-suppressor role. Northern blot, pharmacologic demethylation, ectopic GPC3 expression, etoposide apoptosis assay, xenograft growth assay American journal of respiratory cell and molecular biology Medium 12816733
2012 LRP1 mediates Hh-induced endocytosis of the GPC3-Hh complex: GPC3 binds Hh and competes with Patched for Hh binding; Hh binding to GPC3 triggers LRP1-dependent endocytosis and degradation of the GPC3-Hh complex, reducing Hh available for signaling. GPC3 binds LRP1 through its heparan sulfate chains, and this interaction displaces GPC3 from lipid rafts. Co-immunoprecipitation, endocytosis assays, lipid raft fractionation, competition binding assays Journal of cell science High 22467855
2013 GPC3 (and GPC1) physically interact with BMP2 and inhibit BMP2, BMP4, and BMP7 signaling in human suture mesenchymal cells. This inhibition is independent of GPC3 cell-surface attachment and glycanation (mediated by the core protein), and acts through both SMAD-dependent and SMAD-independent BMP pathways. Immunoblockade of endogenous GPC1 and GPC3 potentiates BMP2 activity, and overexpression inhibits BMP2-mediated osteogenesis. Co-immunoprecipitation (GPC3-BMP2 interaction), recombinant protein addition, overexpression, immunoblockade of endogenous proteins, SMAD signaling assays, osteogenesis assays, GPI-anchor and glycanation-deficient constructs Bone High 23624389
2013 Knockdown of GPC3 in Huh7 HCC cells induces apoptosis and inhibits proliferation, migration, and invasion; GPC3 knockdown suppresses YAP expression at mRNA and protein levels, and addition of recombinant YAP-1 rescues cells from GPC3-knockdown-induced apoptosis, placing GPC3 upstream of YAP in the Hippo pathway. siRNA knockdown, flow cytometry (apoptosis), EdU incorporation (proliferation), migration/invasion assays, qPCR, western blot, recombinant YAP-1 rescue experiment Journal of cellular biochemistry Medium 23060277
2022 Crystal structure of GPC3 in complex with the guidance receptor Unc5D reveals an octameric glycoprotein complex (4 Unc5D + 4 GPC3). Central glycan-glycan interactions are formed between N-linked glycans from GPC3 (N241 in human) and C-mannosylated tryptophans of Unc5D thrombospondin-like domains. Structure-based mutants and nanobodies modulating GPC3-Unc5 binding demonstrate that this complex guides migrating pyramidal neurons in the mouse cortex and cancer cell migration. X-ray crystallography, MD simulations, mass spectrometry, structure-based mutagenesis, anti-GPC3 nanobodies, embryonic xenograft neuroblastoma model, mouse cortex neuron migration assay Cell High 36240740
2014 GPC3 overexpression in renal carcinoma cell lines (786-O and ACHN) reduces cell proliferation through G1-phase cell cycle arrest without inducing apoptosis. GPC3 expression vector transfection, MTT assay, colony formation assay, flow cytometry (cell cycle and apoptosis) BMC cancer Medium 25168166
2018 GPC3 promotes HCC cell proliferation through the Hedgehog (Hh) pathway in HepG2 cells (but not HLE cells), as shown by in vitro analysis of GPC3-overexpressing cell lines. Overexpression in HCC cell lines, RT-PCR, cell proliferation assay, Hedgehog pathway gene expression analysis Oncology letters Low 29963171
2013 Overexpression of GPC3 in Huh7 and SK-HEP-1 HCC cells inhibits proliferation and invasion through induction of apoptosis; co-treatment with IGF2 and FGF2 significantly inhibits GPC3-induced apoptotic cell death, indicating GPC3 acts as a negative regulator of IGF2 and FGF2 pathways. Transfection, Annexin V-PI flow cytometry, IGF2/FGF2 co-treatment rescue experiment Molecular medicine reports Medium 23338845
2023 GPC3 structural analysis predicts that the Furin cleavage site of GPC3 is exposed and accessible, facilitating cleavage events. Furin-dependent GPC3 cleaved domains were detected in serum small extracellular vesicles (sEVs) isolated from HCC patients. In silico structural prediction, isolation of sEVs from patient serum and hepatocyte culture media, western blotting for GPC3 domains International journal of molecular sciences Low 37446098
2001 GPC3 protein is expressed in human placenta and localizes specifically to the differentiated syncytiotrophoblast layer, as confirmed by in situ hybridization and immunohistochemistry; cytotrophoblasts increase GPC3 expression during trophoblast differentiation, while fibroblasts and choriocarcinoma lines do not express GPC3. In situ hybridization, immunohistochemistry, RT-PCR in cell lines and primary cultures Histology and histopathology Medium 11193214

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nature genetics 613 8589713
2008 Human SGBS cells - a unique tool for studies of human fat cell biology. Obesity facts 226 20054179
2017 Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carcinoma. Frontiers in immunology 190 28123387
2024 Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers. Nature 178 39604730
2017 Development of GPC3-Specific Chimeric Antigen Receptor-Engineered Natural Killer Cells for the Treatment of Hepatocellular Carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 157 29339014
2005 Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed and secreted by human (SGBS) adipocytes. FEBS letters 152 15620688
1999 Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer research 150 10029067
1998 OCI-5/GPC3, a glypican encoded by a gene that is mutated in the Simpson-Golabi-Behmel overgrowth syndrome, induces apoptosis in a cell line-specific manner. The Journal of cell biology 139 9628896
2019 Combined Antitumor Effects of Sorafenib and GPC3-CAR T Cells in Mouse Models of Hepatocellular Carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 138 31078430
2000 Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma. Oncogene 127 10656689
2016 Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3. The FEBS journal 121 27573079
1997 OCI-5/rat glypican-3 binds to fibroblast growth factor-2 but not to insulin-like growth factor-2. The Journal of biological chemistry 117 9065409
2008 Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development. Histology and histopathology 102 18785116
2000 Mutational analysis of the GPC3/GPC4 glypican gene cluster on Xq26 in patients with Simpson-Golabi-Behmel syndrome: identification of loss-of-function mutations in the GPC3 gene. Human molecular genetics 95 10814714
2000 Expression of glypican 3 (GPC3) in embryonal tumors. International journal of cancer 91 11008203
2021 A bispecific antibody targeting GPC3 and CD47 induced enhanced antitumor efficacy against dual antigen-expressing HCC. Molecular therapy : the journal of the American Society of Gene Therapy 90 33429083
2001 GPC3 mutation analysis in a spectrum of patients with overgrowth expands the phenotype of Simpson-Golabi-Behmel syndrome. American journal of medical genetics 89 11477610
1998 Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome. Developmental dynamics : an official publication of the American Association of Anatomists 89 9853964
2003 The heparan sulfate proteoglycan GPC3 is a potential lung tumor suppressor. American journal of respiratory cell and molecular biology 83 12816733
2013 Phenotypic spectrum of Simpson-Golabi-Behmel syndrome in a series of 42 cases with a mutation in GPC3 and review of the literature. American journal of medical genetics. Part C, Seminars in medical genetics 72 23606591
1998 GPC4, the gene for human K-glypican, flanks GPC3 on xq26: deletion of the GPC3-GPC4 gene cluster in one family with Simpson-Golabi-Behmel syndrome. Genomics 71 9787072
2022 GPC3-targeted immunoPET imaging of hepatocellular carcinomas. European journal of nuclear medicine and molecular imaging 69 35147737
2020 DNAM1 and 2B4 Costimulatory Domains Enhance the Cytotoxicity of Anti-GPC3 Chimeric Antigen Receptor-Modified Natural Killer Cells Against Hepatocellular Cancer Cells in vitro. Cancer management and research 69 32440221
2016 GPC-3 in hepatocellular carcinoma: current perspectives. Journal of hepatocellular carcinoma 69 27878117
2022 Selenium nanoparticles overcomes sorafenib resistance in thioacetamide induced hepatocellular carcinoma in rats by modulation of mTOR, NF-κB pathways and LncRNA-AF085935/GPC3 axis. Life sciences 64 35640776
2019 Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors. Frontiers in oncology 60 30873384
2020 Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention. Hepatology (Baltimore, Md.) 54 31520528
2017 SGBS cells as a model of human adipocyte browning: A comprehensive comparative study with primary human white subcutaneous adipocytes. Scientific reports 53 28642596
2023 Bispecific GPC3/PD‑1 CAR‑T cells for the treatment of HCC. International journal of oncology 51 36896779
2018 Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma. Drug delivery 51 29916268
2023 GPC3-IL7-CCL19-CAR-T primes immune microenvironment reconstitution for hepatocellular carcinoma therapy. Cell biology and toxicology 48 37853185
2017 Significance of Glypican-3 (GPC3) Expression in Hepatocellular Cancer Diagnosis. Medical science monitor : international medical journal of experimental and clinical research 48 28207681
2013 Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3. Bone 47 23624389
2018 DEHP deregulates adipokine levels and impairs fatty acid storage in human SGBS-adipocytes. Scientific reports 46 29472605
2018 HOXA-AS2 Promotes Proliferation and Induces Epithelial-Mesenchymal Transition via the miR-520c-3p/GPC3 Axis in Hepatocellular Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 46 30415263
1999 Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome. American journal of human genetics 46 10441586
2016 Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase. Biochimica et biophysica acta 45 26968895
2013 Knockdown of GPC3 inhibits the proliferation of Huh7 hepatocellular carcinoma cells through down-regulation of YAP. Journal of cellular biochemistry 45 23060277
2012 LRP1 mediates Hedgehog-induced endocytosis of the GPC3-Hedgehog complex. Journal of cell science 45 22467855
2010 Evaluation for clinical utility of GPC3, measured by a commercially available ELISA kit with Glypican-3 (GPC3) antibody, as a serological and histological marker for hepatocellular carcinoma. Hepatology research : the official journal of the Japan Society of Hepatology 45 20374302
2024 Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma. Molecular therapy. Oncology 44 38882528
2022 20 Years with SGBS cells - a versatile in vitro model of human adipocyte biology. International journal of obesity (2005) 42 35986215
2017 Codelivery of sorafenib and GPC3 siRNA with PEI-modified liposomes for hepatoma therapy. Biomaterials science 41 29106433
2016 Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes. Nutrients 41 27187453
1999 DNA methylation in transcriptional repression of two differentially expressed X-linked genes, GPC3 and SYBL1. Proceedings of the National Academy of Sciences of the United States of America 41 9892682
2017 Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager. Oncotarget 40 28881778
2001 Glypican-3 (GPC3) expression in human placenta: localization to the differentiated syncytiotrophoblast. Histology and histopathology 40 11193214
1997 Expression of OCI-5/glypican 3 during intestinal morphogenesis: regulation by cell shape in intestinal epithelial cells. Experimental cell research 38 9281346
2022 GPC3-Unc5 receptor complex structure and role in cell migration. Cell 36 36240740
2022 GPC3-targeted CAR-T cells secreting B7H3-targeted BiTE exhibit potent cytotoxicity activity against hepatocellular carcinoma cell in the in vitro assay. Biochemistry and biophysics reports 35 36032401
2011 Expression of GPC3 protein and its significance in lung squamous cell carcinoma. Medical oncology (Northwood, London, England) 35 21556932
2019 Differentiating SGBS adipocytes respond to PPARγ stimulation, irisin and BMP7 by functional browning and beige characteristics. Scientific reports 34 30967578
2011 HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes. Antiviral therapy 34 22301094
2014 GPC3 reduces cell proliferation in renal carcinoma cell lines. BMC cancer 33 25168166
2024 GPC3-targeted CAR-T cells expressing GLUT1 or AGK exhibit enhanced antitumor activity against hepatocellular carcinoma. Acta pharmacologica Sinica 32 38750075
2011 THP-1 Macrophages and SGBS Adipocytes - A New Human in vitro Model System of Inflamed Adipose Tissue. Frontiers in endocrinology 32 22645513
2003 Genotype/phenotype correlations of males affected by Simpson-Golabi-Behmel syndrome with GPC3 gene mutations: patient report and review of the literature. Journal of pediatric endocrinology & metabolism : JPEM 32 12713262
2018 Phosphorothioate-Modified AP613-1 Specifically Targets GPC3 when Used for Hepatocellular Carcinoma Cell Imaging. Molecular therapy. Nucleic acids 31 30347351
2018 An innovative peptide with high affinity to GPC3 for hepatocellular carcinoma diagnosis. Biomaterials science 31 30417190
2012 The SGBS cell strain as a model for the in vitro study of obesity and cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 31 22855155
2020 Radiofluorinated GPC3-Binding Peptides for PET Imaging of Hepatocellular Carcinoma. Molecular imaging and biology 30 31044341
2010 Familial Simpson-Golabi-Behmel syndrome: studies of X-chromosome inactivation and clinical phenotypes in two female individuals with GPC3 mutations. Clinical genetics 30 20950395
2022 BOXR1030, an anti-GPC3 CAR with exogenous GOT2 expression, shows enhanced T cell metabolism and improved anti-cell line derived tumor xenograft activity. PloS one 29 35507536
2022 Simultaneous Homogeneous Fluorescence Detection of AFP and GPC3 in Hepatocellular Carcinoma Clinical Samples Assisted by Enzyme-Free Catalytic Hairpin Assembly. ACS applied materials & interfaces 29 35699181
2021 Co-expression of IL-7 and PH20 promote anti-GPC3 CAR-T tumour suppressor activity in vivo and in vitro. Liver international : official journal of the International Association for the Study of the Liver 29 33347692
2015 Inhibition of adipogenic differentiation of human SGBS preadipocytes by androgen-regulated microRNA miR-375. Molecular and cellular endocrinology 29 26219823
2013 Hypoxia induces a HIF-1α dependent signaling cascade to make a complex metabolic switch in SGBS-adipocytes. Molecular and cellular endocrinology 29 24275182
2017 The Value of GPC3 and GP73 in Clinical Diagnosis of Hepatocellular Carcinoma. Clinical laboratory 27 29226636
1997 Analysis of exon/intron structure and 400 kb of genomic sequence surrounding the 5'-promoter and 3'-terminal ends of the human glypican 3 (GPC3) gene. Genomics 27 9339360
2020 A novel targeted GPC3/CD3 bispecific antibody for the treatment hepatocellular carcinoma. Cancer biology & therapy 26 32240054
2020 Preparation and Characterization of Anti-GPC3 Nanobody Against Hepatocellular Carcinoma. International journal of nanomedicine 26 32280214
2023 Targeting GPC3high cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in gastric cancer. Annals of medicine 25 37036308
2018 miR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells. Oncology letters 25 29805640
2008 Characterisation of aromatase expression in the human adipocyte cell line SGBS. Breast cancer research and treatment 25 18181018
2018 Low glucose metabolism in hepatocellular carcinoma with GPC3 expression. World journal of gastroenterology 24 29398870
2015 Differential expression of glypican-3 (GPC3) in lung squamous cell carcinoma and lung adenocarcinoma and its clinical significance. Genetics and molecular research : GMR 24 26345955
2013 Overexpression of GPC3 inhibits hepatocellular carcinoma cell proliferation and invasion through induction of apoptosis. Molecular medicine reports 24 23338845
2019 ELK1-activated GPC3-AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells. The journal of gene medicine 23 31168873
2022 Chimeric anti-GPC3 sFv-CD3ε receptor-modified T cells with IL7 co-expression for the treatment of solid tumors. Molecular therapy oncolytics 22 35572194
2018 Elevated GPC3 level promotes cell proliferation in liver cancer. Oncology letters 22 29963171
2014 Critical analysis of the potential of targeting GPC3 in hepatocellular carcinoma. Journal of hepatocellular carcinoma 22 27508174
1997 Cloning and characterization of human cDNAs encoding a protein with high homology to rat intestinal development protein OCI-5. Gene 22 9133586
2023 Derivation and Preclinical Characterization of CYT-303, a Novel NKp46-NK Cell Engager Targeting GPC3. Cells 21 37048069
2020 Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression. International journal of molecular sciences 20 33076548
2018 Mutation update for the GPC3 gene involved in Simpson-Golabi-Behmel syndrome and review of the literature. Human mutation 20 29637653
2018 Role of 1α,25-Dihydroxyvitamin D3 in Adipogenesis of SGBS Cells: New Insights into Human Preadipocyte Proliferation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 30016791
2024 GPC3-targeted CAR-M cells exhibit potent antitumor activity against hepatocellular carcinoma. Biochemistry and biophysics reports 19 38881757
2021 The clinical significance of CTC enrichment by GPC3-IML and its genetic analysis in hepatocellular carcinoma. Journal of nanobiotechnology 19 33726759
2014 Somatic CTNNB1 mutation in hepatoblastoma from a patient with Simpson-Golabi-Behmel syndrome and germline GPC3 mutation. American journal of medical genetics. Part A 19 24459012
2024 Interleukin-15-armored GPC3-CAR T cells for patients with solid cancers. Research square 18 38645165
2023 Liraglutide demonstrates a therapeutic effect on mitochondrial dysfunction in human SGBS adipocytes in vitro. Diabetes research and clinical practice 18 36958431
2024 20(S)-Ginsenoside Rh2 inhibits hepatocellular carcinoma by suppressing angiogenesis and the GPC3-mediated Wnt/β‑catenin signaling pathway. Acta biochimica et biophysica Sinica 17 38584523
2023 Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients. International journal of molecular sciences 17 37446098
2022 Identification of miR-4510 as a metastasis suppressor of gastric cancer through regulation of tumor microenvironment via targeting GPC3. Clinical & experimental metastasis 17 35050429
2021 Development of GPC3 and EGFR-dual-targeting chimeric antigen receptor-T cells for adoptive T cell therapy. American journal of translational research 17 33527015
2014 GPC3 DNA vaccine elicits potent cellular antitumor immunity against HCC in mice. Hepato-gastroenterology 17 24901124
2023 HMGB1/GPC3 dual targeting vaccine induces dendritic cells-mediated CD8+T cell immune response and elicits potential therapeutic effect in hepatocellular carcinoma. iScience 16 36879804
2021 Combination of AAV-CCL19 and GPC3 CAR-T Cells in the Treatment of Hepatocellular Carcinoma. Journal of immunology research 16 34527749
2024 GPC-3 in hepatocellular carcinoma; A novel biomarker and molecular target. Experimental cell research 15 39725192
2020 In Depth Quantitative Proteomic and Transcriptomic Characterization of Human Adipocyte Differentiation using the SGBS Cell Line. Proteomics 15 32384580

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