Affinage

GPC3

Glypican-3 · UniProt P51654

Length
580 aa
Mass
65.6 kDa
Annotated
2026-04-28
100 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPC3 encodes glypican-3, a GPI-anchored heparan sulfate proteoglycan that functions as a multivalent signaling hub controlling cell growth, apoptosis, and migration by modulating several major pathways. GPC3 forms complexes with IGF2 and FGF2 to negatively regulate their mitogenic signaling (PMID:8589713, PMID:23338845), binds Hedgehog ligands and triggers their LRP1-dependent endocytosis and degradation through its heparan sulfate chains to inhibit Hh–Patched signaling (PMID:22467855), inhibits canonical Wnt/β-catenin signaling by extracellular sequestration of Wnt ligands while activating p38 MAPK to suppress metastasis and promote tumor dormancy (PMID:30267212, PMID:32800275), and modulates Hippo pathway output through YAP (PMID:23060277). GPC3 also forms a structurally defined octameric complex with the guidance receptor Unc5D via glycan–glycan interactions that directs cortical neuron migration and cancer cell migration in vivo (PMID:36240740). The GPC3 promoter is Sp1-dependent and subject to CpG island hypermethylation-mediated silencing in mesothelioma, ovarian, lung, and breast cancers, where GPC3 re-expression suppresses colony formation and tumor growth, consistent with its role as a tumor suppressor in these contexts (PMID:9651473, PMID:10029067, PMID:10656689, PMID:12816733).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1996 Medium

    The identity of GPC3 as a GPI-anchored heparan sulfate proteoglycan that binds IGF2 provided the first molecular framework for how it might control mesodermal growth.

    Evidence Western blotting and ligand blotting in transfected cells

    PMID:8589713

    Open questions at the time
    • IGF2 binding affinity and stoichiometry not determined
    • Functional consequence of GPC3–IGF2 interaction on downstream signaling not tested
    • Single pulldown/blotting approach without reciprocal validation
  2. 1997 Medium

    Demonstration that GPC3 transcription is regulated by cell shape established that its expression is dynamically controlled by the physical microenvironment of epithelial cells.

    Evidence Nuclear run-on assays and pharmacological perturbations of cell shape in intestinal epithelial cells

    PMID:9281346

    Open questions at the time
    • Transcription factor(s) mediating shape-dependent regulation not identified
    • Relevance to in vivo tissue architecture unknown
  3. 1998 High

    Identification of Sp1 as the direct transcriptional driver of the TATA-less GPC3 promoter and demonstration that GPC3 induces apoptosis in a GPI-anchor-dependent manner (rescued by IGF2) established its dual identity as a transcriptionally regulated growth suppressor.

    Evidence DNase I footprinting, EMSA/supershift, Sp1-deficient SL2 cell reporter assay (promoter); ectopic expression with GPI-anchor and HS-chain mutants, apoptosis assays, IGF2 rescue (function)

    PMID:9628896 PMID:9651473

    Open questions at the time
    • Downstream apoptotic pathway (caspase dependence, death receptor involvement) not delineated
    • Why GPI anchor is essential but HS chains dispensable for apoptosis induction not explained
  4. 1999 Medium

    Discovery that promoter CpG island hypermethylation silences GPC3 in ovarian cancer, with demethylation restoring expression and re-expression suppressing colony formation, established the epigenetic tumor suppressor paradigm for GPC3.

    Evidence Southern blot methylation analysis, 5-aza-CdR demethylation, colony-forming assay in ovarian cancer lines; in vitro methylation-reporter assay and allele-specific methylation analysis

    PMID:10029067 PMID:9892682

    Open questions at the time
    • Methyltransferases responsible for silencing not identified
    • Whether methylation-based silencing occurs at the same frequency in primary tumors vs. cell lines not established
  5. 2000 Medium

    Extension of the methylation-silencing mechanism to mesothelioma, and later to lung cancer (with in vivo xenograft validation), broadened GPC3's tumor suppressor role across epithelial malignancies.

    Evidence Methylation analysis, 5-aza-CdR demethylation, colony assay (mesothelioma); pharmacologic demethylation, ectopic expression, nude mouse xenograft, etoposide sensitization (lung cancer)

    PMID:10656689 PMID:12816733

    Open questions at the time
    • Mechanism by which GPC3 sensitizes cells to etoposide-induced apoptosis not defined
    • No genetic loss-of-function models in vivo
  6. 2012 High

    Elucidation of the LRP1-mediated endocytic clearance mechanism showed how GPC3 inhibits Hedgehog signaling: GPC3 binds Hh via its core protein, then its HS chains recruit LRP1, which internalizes and degrades the GPC3–Hh complex away from Patched.

    Evidence Co-immunoprecipitation, endocytosis assays, HS-chain mutants, lipid raft fractionation, siRNA knockdown of LRP1

    PMID:22467855

    Open questions at the time
    • Whether all three Hedgehog ligands (Shh, Ihh, Dhh) are equally cleared is untested
    • In vivo validation of the LRP1-dependent clearance mechanism not provided
    • Structural basis of GPC3–Hh recognition not determined
  7. 2013 Medium

    Positioning GPC3 upstream of YAP in HCC cells and demonstrating its negative regulation of both IGF2 and FGF2 survival pathways expanded the roster of signaling axes controlled by GPC3 beyond Hedgehog.

    Evidence siRNA knockdown with YAP rescue in Huh7 cells; ectopic GPC3 expression with IGF2/FGF2 rescue in HCC cells

    PMID:23060277 PMID:23338845

    Open questions at the time
    • Whether GPC3 acts on YAP through canonical Hippo kinase cascade or an alternative route is unknown
    • Direct physical interaction between GPC3 and FGF2 not demonstrated
    • Context-dependent pro- vs. anti-growth roles in HCC not reconciled
  8. 2018 Medium

    Demonstration that GPC3 inhibits canonical Wnt signaling by extracellular sequestration of Wnt ligands while simultaneously activating p38 MAPK to shift the ERK/p38 ratio toward dormancy revealed a dual-pathway mechanism for metastasis suppression.

    Evidence Wnt luciferase reporters, conditioned medium experiments, GSK3β inhibitor rescue, wound-healing assays in breast cancer cells; in vivo metastasis assay with pharmacologic p38 inhibition

    PMID:30267212 PMID:32800275

    Open questions at the time
    • Identity of the specific Wnt ligands sequestered by GPC3 not determined
    • Whether p38 activation is direct or mediated through an intermediary receptor is unknown
    • Single-lab findings; independent replication pending
  9. 2022 High

    Crystallographic resolution of the GPC3–Unc5D octameric complex, mediated by glycan–glycan interactions, revealed a structural mechanism by which GPC3 guides cortical neuron and cancer cell migration, establishing its first atomic-resolution functional model.

    Evidence X-ray crystallography, MD simulations, mass spectrometry, structure-based mutagenesis, anti-GPC3 nanobodies, in vivo cortical migration and embryonic neuroblastoma xenograft assays

    PMID:36240740

    Open questions at the time
    • Whether the GPC3–Unc5D complex transduces intracellular signaling through Unc5D's death domain is not addressed
    • Relevance of the octameric complex to GPC3's tumor suppressor function in epithelial cancers is unexplored
    • Contribution of heparan sulfate chains vs. N-glycans to complex stability not fully parsed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GPC3 integrates its multiple signaling outputs (Hh, Wnt, IGF2, FGF2, p38, YAP, Unc5D) in a context-dependent manner — acting as tumor suppressor in some tissues and oncogene in HCC — remains unresolved.
  • No unified signaling model explaining tissue-specific tumor suppressor vs. oncogenic function
  • No conditional genetic knockout studies dissecting individual pathway contributions in vivo
  • Structural basis for GPC3–Wnt and GPC3–IGF2 interactions not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 1
Partners
FGF2IGF2LRP1SP1UNC5DYAP1
Complex memberships
GPC3–Hedgehog–LRP1 endocytic complexGPC3–Unc5D octameric complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 GPC3 encodes a heparan sulfate proteoglycan (glypican-3) anchored to the extracellular surface, and initial western- and ligand-blotting experiments showed it forms a complex with IGF2, suggesting it modulates IGF2 action to control embryonic mesodermal growth. Western blotting and ligand blotting Nature genetics Medium 8589713
1998 GPC3 (OCI-5) induces apoptosis in a cell-type-specific manner (mesothelioma and breast cancer cells but not NIH 3T3 or HT-29 cells); this apoptotic activity requires GPI membrane anchoring but not the heparan sulfate glycosaminoglycan chains. IGF2 rescues MCF-7 cells from GPC3-induced apoptosis. Ectopic expression, apoptosis assays, GPI-anchor and glycosaminoglycan chain mutants, IGF2 rescue experiment The Journal of cell biology High 9628896
1997 OCI-5/GPC3 expression in intestinal epithelial cells is regulated transcriptionally by cell shape: rounding of cells (confluence, low calcium, spheroid culture) increases OCI-5 transcription, while cell flattening (colchicine) or phosphatase inhibition (vanadate) suppresses it. RNA in situ hybridization, nuclear run-on transcription assays, pharmacological perturbations of cell shape Experimental cell research Medium 9281346
1998 The GPC3 promoter is TATA-less and driven by multiple Sp1 binding sites; three Sp1 sites (centered at –14, –34, and –92 nt) are functional as shown by DNase I footprinting and gel-shift/supershift assays, and Sp1 transactivates GPC3 in Sp1-deficient Drosophila SL2 cells. Deletion analysis, luciferase reporter assay, DNase I footprinting, EMSA/supershift, transfection in Sp1-deficient SL2 cells Gene High 9651473
1999 GPC3 expression is silenced in ovarian cancer cell lines by promoter hypermethylation; demethylation with 5-aza-2'-deoxycytidine restores expression, and ectopic GPC3 expression inhibits colony formation, supporting a tumor suppressor function in the ovary. Southern blot methylation analysis, 5-aza-CdR demethylation, colony-forming assay with ectopic GPC3 Cancer research Medium 10029067
1999 The GPC3 promoter CpG island is subject to X-chromosome inactivation-induced hypermethylation on the inactive X allele; in vitro methylation of the GPC3 promoter represses reporter gene transcription, while tissue-specific repression on the active X does not involve promoter methylation. Reporter assay with in vitro methylated promoter constructs, Southern blot analysis of allele-specific methylation, azadeoxycytidine demethylation Proceedings of the National Academy of Sciences of the United States of America Medium 9892682
2000 GPC3 is silenced in malignant mesothelioma primarily by promoter hypermethylation (not mutation or allelic loss); ectopic GPC3 expression inhibits in vitro colony formation of human MM cells, indicating a growth-suppressive function. Northern blot, methylation analysis, 5-aza-CdR demethylation, ectopic expression colony assay Oncogene Medium 10656689
2003 GPC3 acts as a lung tumor suppressor; its expression is epigenetically silenced by promoter hypermethylation in non-small cell lung carcinoma lines, and ectopic GPC3 expression increases apoptosis in response to etoposide and inhibits tumor growth in nude mice. Pharmacologic demethylation, ectopic expression, xenograft assay, apoptosis assay American journal of respiratory cell and molecular biology Medium 12816733
2012 LRP1 mediates Hedgehog-induced endocytosis of the GPC3-Hh complex; GPC3 binds Hh and competes with Patched (Ptc) for Hh binding. The GPC3-Hh interaction triggers LRP1-dependent internalization and degradation of the complex, reducing Hh available for Ptc binding. GPC3 binds LRP1 through its heparan sulfate chains, and this interaction displaces GPC3 from lipid raft domains. Co-immunoprecipitation, endocytosis assays, heparan sulfate chain mutants, lipid raft fractionation, siRNA knockdown of LRP1 Journal of cell science High 22467855
2013 GPC3 knockdown in Huh7 hepatocellular carcinoma cells induces apoptosis and inhibits proliferation, migration, and invasion, accompanied by suppression of YAP mRNA and protein; addition of recombinant YAP-1 rescues cells from GPC3 knockdown-induced apoptosis, placing GPC3 upstream of Hippo pathway effector YAP. siRNA knockdown, flow cytometry apoptosis assay, EdU proliferation assay, qPCR, Western blot, recombinant YAP-1 rescue Journal of cellular biochemistry Medium 23060277
2016 The lncRNA GPC3-AS1 physically associates with the histone acetyltransferase P300/CBP-associated factor (PCAF) and recruits it to the GPC3 gene body, increasing euchromatic histone marks and activating GPC3 transcription; GPC3-AS1-driven HCC cell proliferation and migration are dependent on upregulation of GPC3. RNA immunoprecipitation (RIP), ChIP, gain- and loss-of-function assays, xenograft The FEBS journal Medium 27573079
2018 In breast cancer cells, GPC3 inhibits the canonical Wnt/β-catenin pathway both transcriptionally and by secretion into extracellular media where it competes with or sequesters Wnt ligands from Frizzled receptors. GPC3 also activates non-canonical Wnt and p38 MAPK pathways; the p38/ERK balance is shifted toward p38, driving dormancy. Inhibition of canonical Wnt by GPC3 is required for its effects on cell migration and homotypic adhesion. Luciferase reporter assay for Wnt activity, Western blotting, qRT-PCR microarray, conditioned medium experiments, lithium (GSK3β inhibitor) rescue, wound-healing and suspension growth assays Journal of cancer research and clinical oncology Medium 30267212
2020 GPC3 re-expression in murine breast cancer cells reverts epithelial-to-mesenchymal transition, reduces the phospho-ERK/phospho-p38 ratio, elevates p21, p27, and SOX2 (dormancy markers), and suppresses metastasis in vivo. In vivo inhibition of p38 increases invasion and experimental metastasis of GPC3-re-expressing tumors, demonstrating that GPC3 inhibits metastasis specifically through p38 MAPK pathway activation. Genetically modified cell lines, Western blotting, in vivo metastasis assays, pharmacologic p38 inhibition European journal of cell biology Medium 32800275
2022 Crystal structures of Unc5D in complex with GPC3 reveal an octameric glycoprotein complex in which four Unc5D molecules form an antiparallel bundle flanked by four GPC3 molecules; central glycan-glycan interactions are formed by N-linked glycans from GPC3 (N241) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. Structure-based mutants and anti-GPC3 nanobodies that modulate Unc5-GPC3 binding demonstrate that this complex guides migrating pyramidal neurons in the mouse cortex and directs cancer cell migration in an embryonic neuroblastoma xenograft model. X-ray crystallography, MD simulations, mass spectrometry, structure-based mutagenesis, anti-GPC3 nanobodies, in vivo cortical neuron migration assay, embryonic xenograft neuroblastoma model Cell High 36240740
2014 GPC3 overexpression in renal cell carcinoma cell lines (786-O and ACHN) reduces cell proliferation by inducing G1 phase cell cycle arrest without triggering apoptosis. Ectopic expression, MTT assay, colony formation, flow cytometry cell cycle analysis BMC cancer Low 25168166
2013 GPC3 overexpression in Huh7 and SK-HEP-1 HCC cells inhibits proliferation and invasion by inducing apoptosis; co-treatment with IGF2 or FGF2 significantly suppresses GPC3-induced apoptosis, indicating GPC3 acts as a negative regulator of IGF2 and FGF2 survival pathways. Ectopic GPC3 expression, Annexin V-PI flow cytometry, IGF2/FGF2 rescue Molecular medicine reports Medium 23338845
2001 GPC3 mRNA and protein are specifically localized to the differentiated syncytiotrophoblast layer of the human placenta, as determined by in situ hybridization and immunohistochemical staining; expression increases markedly during cytotrophoblast differentiation into syncytiotrophoblast in vitro. In situ hybridization, immunohistochemistry, RT-PCR during in vitro differentiation Histology and histopathology Low 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 610 8589713
2008 Human SGBS cells - a unique tool for studies of human fat cell biology. Obesity facts 226 20054179
2024 Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers. Nature 161 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 153 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
2016 Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients. Oncoimmunology 141 27467945
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 136 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
2002 Utilization of L-ascorbate by Escherichia coli K-12: assignments of functions to products of the yjf-sga and yia-sgb operons. Journal of bacteriology 104 11741871
2008 Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development. Histology and histopathology 102 18785116
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 88 33429083
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
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 68 32440221
2016 GPC-3 in hepatocellular carcinoma: current perspectives. Journal of hepatocellular carcinoma 67 27878117
2022 GPC3-targeted immunoPET imaging of hepatocellular carcinomas. European journal of nuclear medicine and molecular imaging 66 35147737
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 63 35640776
2019 Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors. Frontiers in oncology 56 30873384
2020 Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention. Hepatology (Baltimore, Md.) 53 31520528
2010 Identification of novel human adipocyte secreted proteins by using SGBS cells. Journal of proteome research 50 20681635
2018 Engineering a bispecific antibody with a common light chain: Identification and optimization of an anti-CD3 epsilon and anti-GPC3 bispecific antibody, ERY974. Methods (San Diego, Calif.) 49 30326272
2023 Bispecific GPC3/PD‑1 CAR‑T cells for the treatment of HCC. International journal of oncology 48 36896779
2017 Significance of Glypican-3 (GPC3) Expression in Hepatocellular Cancer Diagnosis. Medical science monitor : international medical journal of experimental and clinical research 48 28207681
2023 GPC3-IL7-CCL19-CAR-T primes immune microenvironment reconstitution for hepatocellular carcinoma therapy. Cell biology and toxicology 47 37853185
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
2018 DEHP deregulates adipokine levels and impairs fatty acid storage in human SGBS-adipocytes. Scientific reports 45 29472605
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
2017 Codelivery of sorafenib and GPC3 siRNA with PEI-modified liposomes for hepatoma therapy. Biomaterials science 41 29106433
2001 Glypican-3 (GPC3) expression in human placenta: localization to the differentiated syncytiotrophoblast. Histology and histopathology 41 11193214
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
2019 Propofol-induced miR-219-5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3-mediated Wnt/β-catenin signalling activation. Journal of cellular biochemistry 40 31104336
2016 Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes. Nutrients 40 27187453
2017 Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager. Oncotarget 39 28881778
2013 Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with hepatocellular carcinoma. Hepatobiliary & pancreatic diseases international : HBPD INT 39 23558072
1999 A small interstitial deletion in the GPC3 gene causes Simpson-Golabi-Behmel syndrome in a Dutch-Canadian family. Journal of medical genetics 39 9950367
2022 20 Years with SGBS cells - a versatile in vitro model of human adipocyte biology. International journal of obesity (2005) 38 35986215
1997 Expression of OCI-5/glypican 3 during intestinal morphogenesis: regulation by cell shape in intestinal epithelial cells. Experimental cell research 38 9281346
2013 Diagnostic value of immunohistochemical staining of GP73, GPC3, DCP, CD34, CD31, and reticulin staining in hepatocellular carcinoma. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 36 23686365
2024 Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma. Molecular therapy. Oncology 35 38882528
2022 GPC3-Unc5 receptor complex structure and role in cell migration. Cell 35 36240740
1998 Multiple Sp1 sites efficiently drive transcription of the TATA-less promoter of the human glypican 3 (GPC3) gene. Gene 35 9651473
2020 Glypican-3 (GPC3) inhibits metastasis development promoting dormancy in breast cancer cells by p38 MAPK pathway activation. European journal of cell biology 34 32800275
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
2019 Differentiating SGBS adipocytes respond to PPARγ stimulation, irisin and BMP7 by functional browning and beige characteristics. Scientific reports 32 30967578
2011 Clinical values of AFP, GPC3 mRNA in peripheral blood for prediction of hepatocellular carcinoma recurrence following OLT: AFP, GPC3 mRNA for prediction of HCC. Hepatitis monthly 32 22087143
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
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 31 36032401
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
2018 Phosphorothioate-Modified AP613-1 Specifically Targets GPC3 when Used for Hepatocellular Carcinoma Cell Imaging. Molecular therapy. Nucleic acids 30 30347351
2024 GPC3-targeted CAR-T cells expressing GLUT1 or AGK exhibit enhanced antitumor activity against hepatocellular carcinoma. Acta pharmacologica Sinica 29 38750075
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
2018 An innovative peptide with high affinity to GPC3 for hepatocellular carcinoma diagnosis. Biomaterials science 29 30417190
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
2010 Familial Simpson-Golabi-Behmel syndrome: studies of X-chromosome inactivation and clinical phenotypes in two female individuals with GPC3 mutations. Clinical genetics 29 20950395
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 27 33347692
2017 The Value of GPC3 and GP73 in Clinical Diagnosis of Hepatocellular Carcinoma. Clinical laboratory 27 29226636
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 25 32280214
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
2013 Overexpression of GPC3 inhibits hepatocellular carcinoma cell proliferation and invasion through induction of apoptosis. Molecular medicine reports 24 23338845
2002 Somatic glypican 3 (GPC3) mutations in Wilms' tumour. British journal of cancer 24 12085187
2019 ELK1-activated GPC3-AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells. The journal of gene medicine 23 31168873
2019 808 nm Near-Infrared Light-Excited UCNPs@mSiO2-Ce6-GPC3 Nanocomposites For Photodynamic Therapy In Liver Cancer. International journal of nanomedicine 23 31908456
2018 Low glucose metabolism in hepatocellular carcinoma with GPC3 expression. World journal of gastroenterology 23 29398870
2022 Chimeric anti-GPC3 sFv-CD3ε receptor-modified T cells with IL7 co-expression for the treatment of solid tumors. Molecular therapy oncolytics 21 35572194
2021 Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma. Immunotherapy 21 33525928
2019 Anti-GPC3 Antibody Tagged Cationic Switchable Lipid-Based Nanoparticles for the Co-Delivery of Anti-miRNA27a And Sorafenib in Liver Cancers. Pharmaceutical research 21 31396764
2018 Elevated GPC3 level promotes cell proliferation in liver cancer. Oncology letters 21 29963171
2014 Critical analysis of the potential of targeting GPC3 in hepatocellular carcinoma. Journal of hepatocellular carcinoma 21 27508174
2023 Derivation and Preclinical Characterization of CYT-303, a Novel NKp46-NK Cell Engager Targeting GPC3. Cells 20 37048069
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
2021 The clinical significance of CTC enrichment by GPC3-IML and its genetic analysis in hepatocellular carcinoma. Journal of nanobiotechnology 19 33726759
2020 Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression. International journal of molecular sciences 19 33076548
2012 Differential diagnostic value of GPC3-CD34 combined staining in small liver nodules with diameter less than 3 cm. American journal of clinical pathology 19 22586053
2023 Liraglutide demonstrates a therapeutic effect on mitochondrial dysfunction in human SGBS adipocytes in vitro. Diabetes research and clinical practice 18 36958431
2018 Signaling network involved in the GPC3-induced inhibition of breast cancer progression: role of canonical Wnt pathway. Journal of cancer research and clinical oncology 18 30267212
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
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 16 38584523
2024 Interleukin-15-armored GPC3-CAR T cells for patients with solid cancers. Research square 16 38645165
2021 Combination of AAV-CCL19 and GPC3 CAR-T Cells in the Treatment of Hepatocellular Carcinoma. Journal of immunology research 16 34527749
2020 In Depth Quantitative Proteomic and Transcriptomic Characterization of Human Adipocyte Differentiation using the SGBS Cell Line. Proteomics 15 32384580
2023 HMGB1/GPC3 dual targeting vaccine induces dendritic cells-mediated CD8+T cell immune response and elicits potential therapeutic effect in hepatocellular carcinoma. iScience 14 36879804
2022 Identification of miR-4510 as a metastasis suppressor of gastric cancer through regulation of tumor microenvironment via targeting GPC3. Clinical & experimental metastasis 14 35050429
2021 Combination Therapy of Hepatocellular Carcinoma by GPC3-Targeted Bispecific Antibody and Irinotecan is Potent in Suppressing Tumor Growth in Mice. Molecular cancer therapeutics 14 34725191
2011 A 1 Mb-sized microdeletion Xq26.2 encompassing the GPC3 gene in a fetus with Simpson-Golabi-Behmel syndrome Report, antenatal findings and review. European journal of medical genetics 14 21362501
2018 Combining expression of GPC3 in tumors and CD16 on NK cells from peripheral blood to identify patients responding to codrituzumab. Oncotarget 13 29535817
2015 Whole exome sequencing identifies a novel frameshift mutation in GPC3 gene in a patient with overgrowth syndrome. Gene 13 26321508
2018 Duplications of GPC3 and GPC4 genes in symptomatic female carriers of Simpson-Golabi-Behmel syndrome type 1. European journal of medical genetics 12 30048822