Affinage

EPHB6

Ephrin type-B receptor 6 · UniProt O15197

Length
1021 aa
Mass
110.7 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPHB6 is a catalytically inactive Eph receptor tyrosine kinase that functions as a signaling scaffold in T cell activation, cell adhesion and migration, vascular tone regulation, and tumor suppression. Although devoid of intrinsic kinase activity, EPHB6 undergoes ligand-dependent tyrosine phosphorylation through transphosphorylation by active family members EphB1 and EphB4, and constitutively associates with the adaptor c-Cbl and the Src-family kinase Fyn, enabling downstream engagement of GRB2–RAS–ERK, Abl, and Rac1/JNK pathways (PMID:11713248, PMID:15955811, PMID:20086179, PMID:29700392). In T cells, EPHB6 localizes to TCR–lipid-raft aggregates and is required for ZAP-70, LAT, and MAPK activation; EphB6-knockout mice exhibit impaired T cell responses and, separately, autism-like behavior linked to gut-microbiota-mediated vitamin B6 and dopamine deficits (PMID:15599401, PMID:32819434). EPHB6 acts as a tumor and metastasis suppressor in neuroblastoma, breast cancer, and lung cancer—where its promoter is frequently silenced by DNA hypermethylation—by promoting cell adhesion, restricting MMP expression, modulating mitochondrial fission via ERK–DRP1, and sensitizing cells to apoptosis (PMID:10984508, PMID:20371680, PMID:19234485, PMID:27788485).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 Medium

    Identifying EPHB6 as a T-lineage receptor with tumor-suppressive activity established its initial functional identity, addressing what cell types express it and whether it has growth-regulatory consequences.

    Evidence Flow cytometric immunophenotyping of human thymocytes/T cells; EPHB6 cDNA re-expression in neuroblastoma lines with colony formation and xenograft assays

    PMID:10648835 PMID:10831073 PMID:10984508

    Open questions at the time
    • Mechanism of tumor suppression not identified
    • Only two neuroblastoma lines tested
    • No downstream signaling pathway defined
  2. 2001 High

    Demonstrating that EphB6 is catalytically dead yet becomes tyrosine-phosphorylated via EphB1 transphosphorylation in a ligand-dependent heterocomplex resolved how a kinase-dead receptor could initiate signaling, establishing the transphosphorylation paradigm central to all subsequent EPHB6 biology.

    Evidence Co-IP of EphB1–EphB6, kinase-dead EphB1 mutant controls, phosphotyrosine immunoblotting with ephrin-B1 stimulation; c-Cbl domain-deletion mutant Co-IPs

    PMID:11466354 PMID:11713248

    Open questions at the time
    • Structural basis of the EphB1–EphB6 heterocomplex unknown
    • Whether EphB6 can be transphosphorylated by other Eph kinases (beyond EphB4, shown later) not tested
  3. 2003 High

    Defining EPHB6's selective inhibition of Rac1–JNK but not ERK downstream of the TCR revealed a pathway-specific modulatory role rather than a global signal amplifier, answering how EphB6 shapes T cell fate decisions.

    Evidence Overexpression and dominant-negative EphB6 in Jurkat cells; Rac1 activation pull-down, JNK kinase assay, IL-2 ELISA, thymocyte apoptosis assay

    PMID:12517763

    Open questions at the time
    • Direct molecular link between EphB6 and Rac1 GEF/GAP not identified
    • Dominant-negative approach may have off-target effects on other Eph receptors
  4. 2004 High

    The EphB6-knockout mouse demonstrated that EphB6 is non-redundantly required for T cell responses in vivo, revealing its role in proximal TCR signaling (ZAP-70, LAT, MAPK) and its migration to lipid rafts upon TCR engagement.

    Evidence EphB6 KO mice; T cell proliferation/cytokine assays, EAE model, raft fractionation, phospho-immunoblot for ZAP-70/LAT/MAPK

    PMID:15599401

    Open questions at the time
    • How a kinase-dead receptor facilitates ZAP-70 activation mechanistically is unclear
    • Contribution of reverse signaling through ephrin-B ligands on APCs not dissected
  5. 2005 High

    A biphasic dose–response to ephrin-B2 uncovered EPHB6 as a molecular switch: constitutive Fyn association supports pro-adhesive signaling at low ligand, while high-ligand Src-family-kinase-mediated phosphorylation triggers repulsion, resolving the paradox of EphB6 promoting both adhesion and repulsion.

    Evidence Dose-response adhesion/migration assays, cytoplasmic-domain truncation, Co-IP of Fyn, Src inhibitor treatment

    PMID:15955811

    Open questions at the time
    • Downstream effectors mediating the attractive versus repulsive arms not fully identified
    • Whether Fyn directly phosphorylates EphB6 or acts indirectly not resolved
  6. 2009 Medium

    Linking EphB6 re-expression to reduced MMP7/MMP19 and increased TIMP2 provided a molecular mechanism for its anti-invasive activity in breast cancer, extending the tumor-suppressor paradigm beyond neuroblastoma.

    Evidence EphB6 expression construct in MDA-MB-231/MDA-MB-435/BT549; invasion assay, RT-PCR for MMPs and TIMP2

    PMID:19234485

    Open questions at the time
    • Transcriptional mechanism connecting EphB6 to MMP/TIMP expression not defined
    • No in vivo validation of MMP changes
  7. 2010 High

    Two discoveries solidified EphB6's biological scope: (1) EphB4 transphosphorylates EphB6 to activate c-Cbl–Abl signaling that suppresses breast cancer invasion, and (2) EphB6 loss in vascular smooth muscle increases RhoA-mediated contractility via disrupted ephrin-B reverse signaling through GRIP1, causing hypertension in castrated male mice.

    Evidence EphB6 re-expression in MDA-MB-231, Cbl siRNA, Co-IP, invasion assays; EphB6 KO mice, arterial contractility, RhoA assay, MLC phosphorylation

    PMID:20086179 PMID:20371680 PMID:22223652

    Open questions at the time
    • Identity of the Abl substrate that mediates adhesion not determined
    • Sex-hormone dependence of the vascular phenotype not mechanistically explained
    • How GRIP1 suppresses RhoA not fully delineated
  8. 2016 High

    Establishing that EPHB6 fragments mitochondria via ERK–DRP1 and thereby sensitizes cancer cells to DR5-mediated apoptosis revealed a novel organelle-level effector mechanism for a kinase-dead receptor.

    Evidence EPHB6 overexpression, ERK inhibition, DRP1 dominant-negative/siRNA, mitochondrial imaging, DR5 agonist apoptosis assay

    PMID:27788485

    Open questions at the time
    • Whether mitochondrial fragmentation is relevant in non-cancer cell types unknown
    • Link between EPHB6 and DRP1 phosphorylation may involve intermediate kinases not mapped
  9. 2018 High

    The identification of a GRB2–RAS–ERK–OCT4 axis downstream of EPHB6 explained how the same receptor can promote tumor-initiating cell expansion in triple-negative breast cancer while simultaneously suppressing EMT, clarifying its context-dependent oncogenic versus suppressive roles.

    Evidence Co-IP of EPHB6–GRB2, ERK inhibition, OCT4 knockdown, xenograft models, flow cytometry for TIC markers

    PMID:29700392

    Open questions at the time
    • Mechanism by which EPHB6 simultaneously activates ERK (pro-TIC) yet suppresses EMT is not resolved
    • Whether GRB2 interaction is direct or via transphosphorylation intermediates unclear
  10. 2019 Medium

    Demonstrating that EPHB6 mutations activate EPHA2–JNK–CDH11 and RhoA/FAK to drive paclitaxel resistance identified a gain-of-function mechanism for mutant EPHB6, distinct from loss-of-expression silencing.

    Evidence EPHB6 mutation constructs, JNK inhibition, EPHA2/CDH11 siRNA, drug resistance assays

    PMID:31160603

    Open questions at the time
    • Specific mutations tested represent a limited panel; structural basis for EPHA2 interaction not defined
    • Single study without independent replication
  11. 2020 High

    Two 2020 studies expanded EPHB6 function to gut–brain and lung cancer axes: EphB6 KO mice develop autism-like behavior via gut-microbiota-mediated vitamin B6/dopamine deficits, and CLDN1 upregulates EPHB6 to suppress ERK1/2–SLUG–driven lung cancer stemness and metastasis.

    Evidence Bidirectional fecal microbiota transplant, metabolomics, electrophysiology in KO mice; CLDN1–EPHB6 Co-IP, xenograft, methylation-specific PCR in lung adenocarcinoma

    PMID:32754286 PMID:32819434

    Open questions at the time
    • Mechanism linking EphB6 loss to gut microbiota dysbiosis is unknown
    • Whether the CLDN1–EPHB6 interaction is direct remains uncertain
  12. 2023 Medium

    Proximity proteomics identified EGFR as an EPHB6 interactor that functionally cooperates to enhance cancer cell proliferation, expanding the repertoire of receptor tyrosine kinases that EPHB6 cross-talks with beyond the Eph family.

    Evidence BioID proximity proteomics, Co-IP of EPHB6–EGFR, xenograft tumor assays

    PMID:37392382

    Open questions at the time
    • Nature of the EPHB6–EGFR interaction (direct or scaffolded) not resolved
    • Whether EGFR transphosphorylates EPHB6 (like EphB1/B4) not tested
    • Single study without independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the EphB6 heterocomplex with active Eph kinases, how a kinase-dead receptor is recruited to and activates TCR-proximal signaling, the mechanism connecting EphB6 loss to gut microbiota remodeling, and the rules governing EPHB6's context-dependent pro-tumorigenic versus tumor-suppressive activity.
  • No crystal structure or cryo-EM structure of EphB6 or its heterocomplexes
  • No reconstituted signaling system with purified components
  • Context-dependent ERK activation versus suppression not mechanistically reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 2
Partners
CBLEFNB2EGFREPHA2EPHB1EPHB4FYNGRB2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 EphB6 is catalytically inactive due to alterations in conserved kinase domain residues, yet undergoes inducible tyrosine phosphorylation upon ephrin-B1 stimulation via transphosphorylation by the active kinase EphB1; EphB1 and EphB6 form a stable heterocomplex, and this transphosphorylation requires EphB1 catalytic activity and is ligand-dependent. Co-immunoprecipitation, overexpression of kinase-active/inactive EphB1 mutants, phosphotyrosine immunoblotting in transfected cells The Journal of biological chemistry High 11713248
2001 EphB6 constitutively associates with the proto-oncogene c-Cbl, requiring a functional phosphotyrosine-binding domain on Cbl but not the RING finger ubiquitin-transfer domain. Co-immunoprecipitation, domain-deletion mutants of c-Cbl The Journal of biological chemistry Medium 11713248
2001 Cross-linking of EphB6 together with CD3 in Jurkat T cells triggers general protein tyrosine phosphorylation, alters lymphokine secretion, inhibits proliferation, and induces Fas-mediated apoptosis; EphB6 associates with Cbl, and cross-linking causes Cbl dephosphorylation and dissociation from SHP-1. Antibody cross-linking, phosphotyrosine immunoblotting, Co-IP, apoptosis assays in Jurkat cells Journal of immunology Medium 11466354
2003 EphB6 overexpression in Jurkat T cells and stimulation with ephrin-B1 selectively inhibits TCR-mediated JNK activation but not the MAPK/ERK pathway; this occurs by preventing TCR-induced activation of the small GTPase Rac1, which is required to initiate the JNK cascade. EphB6 also blocks anti-CD3-induced IL-2 secretion and CD25 expression in a ligand-dependent manner, and inhibits TCR-mediated apoptosis in murine thymocytes. Overexpression and dominant-negative EphB6 in Jurkat cells, Rac1 activation assay, JNK kinase assay, cytokine ELISA, thymocyte apoptosis assay The Journal of biological chemistry High 12517763
2004 EphB6-deficient mice show compromised in vitro and in vivo T cell responses (lymphokine secretion, proliferation, delayed-type hypersensitivity, experimental autoimmune encephalitis) while humoral responses remain normal; mechanistically, loss of EphB6 reduces ZAP-70 activation, LAT phosphorylation, PLCγ1-SLP-76 association, and p44/42 MAPK activation downstream of the TCR. EphB6 migrates to aggregated TCRs and lipid rafts after TCR activation. EphB6 knockout mice, T cell proliferation and cytokine assays, EAE model, TCR raft fractionation, phosphoflow/immunoblot for ZAP-70, LAT, PLCγ1, MAPK The Journal of clinical investigation High 15599401
2000 Ephrin-B2 (but not ephrin-B1) is a high-affinity saturable ligand for EphB6; EphB6 binds transmembrane ephrin ligands (not GPI-anchored), and ephrin-B2 is expressed in human and mouse thymus where EphB6 is the dominant ephrin-B2-binding receptor on adult thymocytes. Soluble EphB6-Fc fusion protein binding to transfected COS cells, phosphatidylinositol-specific phospholipase C treatment, binding competition, RT-PCR, EphB6 KO thymocyte binding assay FEBS letters / Biochemical and biophysical research communications High 10648835 12379224
2005 EphB6 exerts biphasic effects on cell adhesion and migration: low concentrations of ephrin-B2 promote adhesion and migration, while high concentrations induce repulsion and inhibit migration. The cytoplasmic domain is required for the negative (repulsive) effects. EphB6 is constitutively associated with the Src-family kinase Fyn, and high ephrin-B2 concentrations induce tyrosine phosphorylation of EphB6 through Src-family kinase activity, acting as a molecular switch. Cell adhesion and migration assays with ephrin-B2 dose-response, cytoplasmic-domain truncation mutant, Co-IP with Fyn, Src kinase inhibitors, phosphotyrosine immunoblotting The Journal of biological chemistry High 15955811
2010 EphB6 restoration in invasive breast cancer cells promotes actin-dependent cell spreading and attachment and blocks invasiveness; EphB6 stimulation induces its tyrosine phosphorylation mediated by the EphB4 receptor (transphosphorylation), accompanied by EphB6-c-Cbl interaction and c-Cbl partner Abl kinase phosphorylation. Cbl silencing suppresses Abl phosphorylation, cell adhesion, and the ability of EphB6 to inhibit invasiveness. EphB6 re-expression in MDA-MB-231 cells, siRNA knockdown of Cbl, invasion assays, Co-IP, phosphotyrosine immunoblotting, actin staining Cancer research High 20086179
2010 EPHB6 expression is silenced by promoter DNA hypermethylation in non-small cell lung cancer; restoration of EPHB6 expression increases cell adhesion, decreases migration, and almost entirely abolishes metastasis formation in NOD/SCID mice. 5-aza-2'-deoxycytidine treatment re-induces EPHB6 expression. Methylation-specific PCR, bisulfite sequencing, 5-azadC demethylation, EPHB6 re-expression, in vitro adhesion/migration assays, in vivo NOD/SCID metastasis model Clinical cancer research High 20371680
2009 EphB6 loss correlates with increased invasiveness in breast cancer cell lines; EphB6 re-expression in MDA-MB-231, MDA-MB-435, and BT549 cells decreases in vitro invasiveness, mediated by decreased MMP7 and MMP19 transcript levels and increased TIMP2 expression. EphB6 expression construct transfection, in vitro invasion assay, RT-PCR for MMP7, MMP19, TIMP2 Oncogene Medium 19234485
2012 EphB6 and its ephrin-B ligands are expressed on vascular smooth muscle cells (VSMC); reverse signaling through ephrin-B ligands (not forward signaling through EphB6) reduces VSMC contraction via GRIP1 adaptor protein. Loss of EphB6 in castrated male mice increases small artery contractility, RhoA activation, and constitutive myosin light chain phosphorylation, leading to elevated blood pressure. EphB6 KO mice, ex vivo arterial contractility assay, RhoA activation assay, myosin light chain phosphorylation, in vitro VSMC cross-linking experiments, 24-h urine catecholamine measurements The Journal of biological chemistry High 22223652
2018 EPHB6 interacts with the GRB2 adapter protein and activates the RAS-ERK pathway to elevate OCT4 expression, thereby promoting expansion of tumor-initiating cells (TICs) in triple-negative breast cancer. Suppression of ERK or OCT4 blocks EPHB6-induced proliferation. EPHB6 also partially suppresses epithelial-mesenchymal transition and sensitizes TICs to DNA-damaging chemotherapy. Co-IP of EPHB6-GRB2, ERK inhibition, OCT4 knockdown, xenograft tumor models, flow cytometry for TIC markers Oncogene High 29700392
2016 EPHB6 induces fragmentation of the mitochondrial network in triple-negative breast cancer cells via activation of the ERK-DRP1 pathway, increasing organelle fission frequency and rendering cells more susceptible to DR5-mediated apoptosis; DRP1 activity is essential to both the mitochondrial fragmentation and the pro-apoptotic response. EPHB6 overexpression, ERK inhibition, DRP1 dominant-negative/siRNA, mitochondrial morphology imaging, DR5 agonist apoptosis assay, DRP1 phosphorylation immunoblot Oncotarget High 27788485
2020 EphB6 deletion in mice induces autism-like behavior and disturbs gut microbiota; the disturbed microbiota leads to vitamin B6 and dopamine deficits. Gut microbiota transplant from EphB6-deficient mice transfers autism-like behavior to antibiotic-treated wild-type mice, and wild-type microbiota transplant rescues behavior in EphB6-KO mice. At the cellular level, gut microbiota-mediated vitamin B6 deficiency regulates the excitation/inhibition balance in the medial prefrontal cortex. EphB6 KO mice, fecal microbiota transplantation, behavioral assays, metabolomics (vitamin B6, dopamine), electrophysiology for E/I balance Microbiome High 32819434
2020 CLDN1 upregulates EPHB6 and enhances its activation, resulting in suppression of ERK1/2 signaling via a CLDN1-EPHB6-ERK1/2-SLUG feedback axis that represses metastasis, drug resistance, and cancer stemness in lung adenocarcinoma. Immunoprecipitation, immunoblotting for ERK1/2 and SLUG, migration assay, sphere assay, aldefluor assay, xenograft experiments, methylation-specific PCR Theranostics Medium 32754286
2019 EPHB6 mutation promotes paclitaxel resistance through interaction with EPHA2, which activates JNK-mediated cadherin 11 (CDH11) expression and RhoA/FAK-dependent cell adhesion-mediated drug resistance (CAM-DR); targeted inhibition of EPHA2 or CDH11 reverses the acquired resistance. EPHB6 mutation-expression constructs, JNK inhibition, EPHA2/CDH11 siRNA, RhoA/FAK phosphorylation immunoblot, drug resistance assays Experimental & molecular medicine Medium 31160603
2017 Enzalutamide-mediated androgen receptor (AR) signaling decreases EPHB6 expression by binding to an androgen-response element (ARE) on the EPHB6 promoter, leading to JNK/MMP9 pathway activation and increased CRPC cell invasion; JNK inhibition reverses this enhanced invasion. ChIP for AR on EPHB6 promoter ARE, luciferase reporter assay, siRNA, invasion assays, JNK phosphorylation immunoblot Cancer letters Medium 28826721
2023 EPHB6 interacts with EGFR (identified by BioID proximity proteomics and confirmed by co-immunoprecipitation) and modulates EGFR signaling to enhance cancer cell proliferation and tumor development. BioID proximity proteomics, Co-IP, genetic interaction screening, xenograft tumor assays Cell reports Medium 37392382
2021 EphB6 promotes survival of disseminated dormant breast cancer cells in the lung by modulating TFEB transcriptional activity and lysosome formation; direct coculture with alveolar type I-like lung epithelial cells and in vivo lung dissemination drive lysosomal accumulation and EphB6 induction; EphB6 also promotes proliferation of surrounding lung parenchymal cells. Lung organotypic system, in vivo dissemination assay, TFEB reporter assay, lysosomal staining, EphB6 knockdown Cancers Medium 33802447
2000 Transfection of EPHB6 cDNA into neuroblastoma cell lines (IMR5 and SY5Y) that express little endogenous EPHB6 inhibits clonogenicity in culture and suppresses tumorigenicity in mouse xenograft models, establishing EPHB6 as a functional suppressor of malignant neuroblastoma phenotype. EPHB6 cDNA transfection, colony formation assay, mouse xenograft tumor model Proceedings of the National Academy of Sciences of the United States of America Medium 10984508
2000 EphB6 is expressed specifically on T-cell lineage hematopoietic cells (CD2+CD7+CD3+CD4+ or CD8+ lymphocytes) and is prominently expressed in CD4+CD8+ double-positive thymocytes, with expression level decreasing with T-cell maturation, as determined by monoclonal antibody staining and flow cytometry. Monoclonal antibody generation, flow cytometry, immunophenotyping of human peripheral blood, bone marrow, and thymocytes Growth factors Medium 10831073

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. The Journal of clinical endocrinology and metabolism 628 2842359
1990 Hep G2 cells as a resource for metabolic studies: lipoprotein, cholesterol, and bile acids. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 318 2153592
1992 Use of HEp-2 cells for improved isolation and passage of Chlamydia pneumoniae. Journal of clinical microbiology 190 1500500
1988 Evidence for targeted gene delivery to Hep G2 hepatoma cells in vitro. Biochemistry 161 2835080
2002 Resveratrol- induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life sciences 127 12409142
2000 Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells. The Journal of nutrition 126 11015487
1989 Adhesion to and invasion of HEp-2 cells by Campylobacter spp. Infection and immunity 126 2550368
1993 Multivesicular bodies in HEp-2 cells are maturing endosomes. European journal of cell biology 125 8223712
2009 Effects of perfluorooctanoate and perfluorooctane sulfonate exposure on hepatoma Hep G2 cells. Archives of toxicology 122 19468714
2001 Motility and the polar flagellum are required for Aeromonas caviae adherence to HEp-2 cells. Infection and immunity 115 11401962
2020 The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice. Microbiome 111 32819434
1992 Adherence and internalization of Helicobacter pylori by HEp-2 cells. Gastroenterology 104 1568565
1988 Re-evaluation of HeLa, HeLa S3, and HEp-2 karyotypes. Cytogenetics and cell genetics 102 3180844
2012 Enhanced biofilm formation by Escherichia coli LPS mutants defective in Hep biosynthesis. PloS one 101 23284671
2000 Implications of EPHB6, EFNB2, and EFNB3 expressions in human neuroblastoma. Proceedings of the National Academy of Sciences of the United States of America 86 10984508
2001 The kinase-null EphB6 receptor undergoes transphosphorylation in a complex with EphB1. The Journal of biological chemistry 82 11713248
2004 EphB6-null mutation results in compromised T cell function. The Journal of clinical investigation 79 15599401
2010 The EphB6 receptor cooperates with c-Cbl to regulate the behavior of breast cancer cells. Cancer research 74 20086179
2010 The EPHB6 receptor tyrosine kinase is a metastasis suppressor that is frequently silenced by promoter DNA hypermethylation in non-small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 74 20371680
2003 Loss of EphB6 expression in metastatic melanoma. International journal of oncology 74 14612926
1994 M protein mediates streptococcal adhesion to HEp-2 cells. Infection and immunity 72 8300205
1991 Penetration and replication of Edwardsiella spp. in HEp-2 cells. Infection and immunity 70 1987028
2004 Acacetin inhibits the proliferation of Hep G2 by blocking cell cycle progression and inducing apoptosis. Biochemical pharmacology 69 15104235
2016 HEp-2 Cell Image Classification With Deep Convolutional Neural Networks. IEEE journal of biomedical and health informatics 68 26887016
1990 A comparison of HEp-2 cell invasion by enteropathogenic and enteroinvasive Escherichia coli. FEMS microbiology letters 67 2199306
1988 Lipid and lipoprotein metabolism in Hep G2 cells. Biochimica et biophysica acta 65 3042028
2005 Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration. The Journal of biological chemistry 64 15955811
1992 Effects of interleukin-6 on the expression of thyroid hormone-binding protein genes in cultured human hepatoblastoma-derived (Hep G2) cells. Molecular endocrinology (Baltimore, Md.) 64 1323058
1996 Internalization of anti-nucleolin antibody into viable HEp-2 cells. Molecular biology reports 62 9112228
2011 Berberine inhibits angiogenic potential of Hep G2 cell line through VEGF down-regulation in vitro. Journal of gastroenterology and hepatology 61 21175812
2009 EphB6 receptor significantly alters invasiveness and other phenotypic characteristics of human breast carcinoma cells. Oncogene 61 19234485
2003 The EphB6 receptor inhibits JNK activation in T lymphocytes and modulates T cell receptor-mediated responses. The Journal of biological chemistry 57 12517763
2001 Cross-linking of EphB6 resulting in signal transduction and apoptosis in Jurkat cells. Journal of immunology (Baltimore, Md. : 1950) 56 11466354
2005 Time dependent modifications of Hep G2 cells during exposure to static magnetic fields. Bioelectromagnetics 55 15832333
1985 Insulin receptors and bioresponses in a human liver cell line (Hep G-2). European journal of biochemistry 50 2410271
1999 Binding of bacteria to HEp-2 cells infected with influenza A virus. FEMS immunology and medical microbiology 47 10225293
1989 An endocytic process in HEp-2 cells induced by enteropathogenic Escherichia coli. Journal of medical microbiology 47 2643705
1997 Resistance to p53-mediated growth arrest and apoptosis in Hep 3B hepatoma cells. Oncogene 46 9233778
2004 Myocilin binding to Hep II domain of fibronectin inhibits cell spreading and incorporation of paxillin into focal adhesions. Experimental cell research 45 15652337
1997 Characterization of group B streptococcal invasion in HEp-2 epithelial cells. FEMS microbiology letters 39 9037766
2000 Ephrin-B2 is a candidate ligand for the Eph receptor, EphB6. FEBS letters 38 10648835
2012 Receptor tyrosine kinase Ephb6 regulates vascular smooth muscle contractility and modulates blood pressure in concert with sex hormones. The Journal of biological chemistry 37 22223652
2011 EphB6 receptor modulates micro RNA profile of breast carcinoma cells. PloS one 37 21811619
2004 Rhein inhibits the growth and induces the apoptosis of Hep G2 cells. Planta medica 37 14765286
2002 Mining knowledge for HEp-2 cell image classification. Artificial intelligence in medicine 36 12234722
1997 Gene therapy of diabetes: glucose-stimulated insulin secretion in a human hepatoma cell line (HEP G2ins/g). Gene therapy 36 9425444
1995 In vitro tumor necrosis factor cytotoxicity in Hep G2 liver cells. Hepatology (Baltimore, Md.) 36 7535734
2018 EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours. Oncogene 35 29700392
2014 Combined treatment with quercetin and imperatorin as a potent strategy for killing HeLa and Hep-2 cells. Molecular and cellular biochemistry 34 24682729
2009 Enantiomer-specific, bifenthrin-induced apoptosis mediated by MAPK signalling pathway in Hep G2 cells. Toxicology 34 19442700
1997 Menadione cytotoxicity to Hep G2 cells and protection by activation of nuclear factor-kappaB. Molecular pharmacology 33 9380028
2002 Hep Par 1 in gastric and bowel carcinomas: an immunohistochemical study. Pathology 32 12408340
2014 Anti-nuclear antibody screening using HEp-2 cells. Journal of visualized experiments : JoVE 31 24998977
2008 The human escort protein Hep binds to the ATPase domain of mitochondrial hsp70 and regulates ATP hydrolysis. The Journal of biological chemistry 31 18632665
2003 Blocking endogenous glypican-3 expression releases Hep 3B cells from G1 arrest. Molecules and cells 31 12872992
1998 Antiproliferative effect of deferiprone on the Hep G2 cell line. Biochemical pharmacology 31 9763218
1994 Oxygen regulation of TGF-beta 1 mRNA in human hepatoma (Hep G2) cells. Biochemistry and molecular biology international 31 7833842
2005 Enhancing effect of taurine on CYP7A1 mRNA expression in Hep G2 cells. Amino acids 30 16151615
1990 Presumptive identification of enteroviruses with RD, HEp-2, and RMK cell lines. Journal of clinical microbiology 30 2161864
2007 Induction of apoptosis by ginger in HEp-2 cell line is mediated by reactive oxygen species. Basic & clinical pharmacology & toxicology 28 17448115
2005 2- and 4-Aminobiphenyls induce oxidative DNA damage in human hepatoma (Hep G2) cells via different mechanisms. Mutation research 28 16112689
2000 T-cell-specific expression of kinase-defective Eph-family receptor protein, EphB6 in normal as well as transformed hematopoietic cells. Growth factors (Chur, Switzerland) 28 10831073
2020 DNA methylation maintains the CLDN1-EPHB6-SLUG axis to enhance chemotherapeutic efficacy and inhibit lung cancer progression. Theranostics 26 32754286
2016 EphB6 overexpression and Apc mutation together promote colorectal cancer. Oncotarget 26 27145271
2002 Developmental expression of EphB6 in the thymus: lessons from EphB6 knockout mice. Biochemical and biophysical research communications 26 12379224
2014 IV Brazilian guidelines for autoantibodies on HEp-2 cells. Revista brasileira de reumatologia 25 24878791
1995 Characteristics of invasion of HEp-2 cells by Providencia alcalifaciens. Journal of medical microbiology 25 7884799
2017 Androgen-deprivation therapy with enzalutamide enhances prostate cancer metastasis via decreasing the EPHB6 suppressor expression. Cancer letters 24 28826721
2013 Peroxiredoxin 3 is resistant to oxidation-induced apoptosis of Hep-3b cells. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 24 24105047
2007 The characteristics of Hep-2 cell with multiple drug resistance induced by Taxol. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 22 17903587
2005 Methotrexate induction of human sulfotransferases in Hep G2 and Caco-2 cells. Journal of applied toxicology : JAT 22 15986412
1995 Comparative effects of clofibrate on peroxisomal enzymes of human (Hep EBNA2) and rat (FaO) hepatoma cell lines. European journal of cell biology 22 7656903
2019 EPHB6 mutation induces cell adhesion-mediated paclitaxel resistance via EPHA2 and CDH11 expression. Experimental & molecular medicine 21 31160603
2010 In vitro cytotoxic activity of Baccharis dracunculifolia and propolis against HEp-2 cells. Natural product research 21 20419558
2011 Cytotoxic activity of artemisinin derivatives against cholangiocarcinoma (CL-6) and hepatocarcinoma (Hep-G2) cell lines. Asian Pacific journal of cancer prevention : APJCP 20 21517231
2008 A dual role of p21waf1/cip1 gene in apoptosis of HEp-2 treated with cisplatin or methotrexate. Cancer gene therapy 20 18483502
2004 Earthworm leukocytes kill HeLa, HEp-2, PC-12 and PA317 cells in vitro. Journal of biochemical and biophysical methods 19 15560938
2020 Deep learning based HEp-2 image classification: A comprehensive review. Medical image analysis 18 32745976
1988 Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s). Journal of cellular physiology 18 2836440
2021 EphB6 Regulates TFEB-Lysosomal Pathway and Survival of Disseminated Indolent Breast Cancer Cells. Cancers 17 33802447
2017 Reduced EphB6 protein in gastric carcinoma and associated lymph nodes suggests EphB6 as a gastric tumor and metastasis inhibitor. Cancer biomarkers : section A of Disease markers 17 28453458
2016 Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells. Toxicology in vitro : an international journal published in association with BIBRA 17 26891812
2012 Lactoferrin and lactoferrin chimera inhibit damage caused by enteropathogenic Escherichia coli in HEp-2 cells. Biochimie 17 22640957
1991 Long term and large-scale cultivation of human hepatoma Hep G2 cells in hollow fiber bioreactor. Cultivation of human hepatoma Hep G2 in hollow fiber bioreactor. Cytotechnology 17 1369306
2025 Hepatitis C Screening in Emergency Departments: The DETECT Hep C Randomized Clinical Trial. JAMA 16 40632510
2015 Expression of EphB6 in ovarian serous carcinoma is associated with grade, TNM stage and survival. Journal of clinical pathology 16 26468391
2010 Trichosanthin affects HSV-1 replication in Hep-2 cells. Biochemical and biophysical research communications 16 20971060
1994 Human phenol sulfotransferases: chiral substrates and expression in Hep G2 cells. Chemico-biological interactions 15 7913418
1988 Isolation and propagation of enteric adenoviruses in HEp-2 cells. Journal of clinical microbiology 15 2844844
1988 In vitro translation and processing of human hepatoma cell (Hep G2) gamma-glutamyl transpeptidase. Biochemical and biophysical research communications 15 2900635
1987 Steady state levels of factor X mRNA in liver and Hep G2 cells. Blood 15 3024758
2023 Integration of cancer-related genetic landscape of Eph receptors and ephrins with proteomics identifies a crosstalk between EPHB6 and EGFR. Cell reports 14 37392382
2019 Oxidative Response and Micronucleus Centromere Assay in HEp-2 Cells Exposed to Fungicide Iprodione. Chemical research in toxicology 14 30702281
2017 Persistence of exhaustion in cured hep C. Blood 14 28684446
2016 The intrinsically kinase-inactive EPHB6 receptor predisposes cancer cells to DR5-induced apoptosis by promoting mitochondrial fragmentation. Oncotarget 14 27788485
2014 Effect of photodynamic therapy supplemented with quercetin in HEp-2 cells. Cell biology international 14 24470266
1999 Effects of doxorubicin, mitomycin C, and ethanol on Hep-G2 cells in vitro. Journal of cancer research and clinical oncology 14 10037271
1997 Genomic organization and mapping of the human HEP-COP gene (COPA) to 1q. Cytogenetics and cell genetics 14 9186507
1996 Complement activation by C-reactive protein on the HEp-2 cell substrate. International archives of allergy and immunology 14 8859218
2014 Apoptosis in HEp-2 cells infected with Ureaplasma diversum. Biological research 13 25299837