Affinage

CEACAM1

Cell adhesion molecule CEACAM1 · UniProt P13688

Length
526 aa
Mass
57.6 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEACAM1 is a multifunctional immunoregulatory transmembrane glycoprotein that broadly dampens activation signals in T cells, NK cells, neutrophils, platelets, and B cells while simultaneously modulating hepatic insulin clearance, cell migration, and pathogen entry. Its inhibitory signaling proceeds through ITIM-dependent recruitment of SHP-1 and SHP-2 phosphatases upon tyrosine phosphorylation of the long cytoplasmic domain (Tyr459/Tyr488), which dephosphorylates downstream effectors such as Vav1, uncouples Shc from receptor tyrosine kinases (insulin receptor, EGFR) to attenuate Ras/MAPK and PI3K/Akt signaling, and suppresses TLR-initiated NF-κB activation (PMID:11493628, PMID:11694516, PMID:18836450, PMID:23696226). CEACAM1 forms obligate cis and trans heterodimers with TIM-3 through its N-terminal IgV domain, is required for TIM-3 surface expression and T cell inhibitory function, and recruits Lck into the immunological synapse of CD8⁺ T cells, positioning it as a dual checkpoint regulator (PMID:25363763, PMID:29967450). The N-terminal domain also serves as a receptor exploited by bacterial adhesins—Neisseria Opa proteins, H. pylori CagA type IV secretion system, and Fusobacterium nucleatum CbpF—to trigger ITIM-mediated immune suppression or facilitate virulence factor injection (PMID:18836450, PMID:30321907, PMID:31069151). Isoform-specific functions are regulated by HIF-1α/Ptbp1-controlled alternative splicing: the short isoform protects hepatocytes from hypoxia-induced ASK1/p-p38 death signaling, while the long isoform in neutrophils restrains NETosis via S1P receptor signaling, collectively governing hepatic ischemia-reperfusion injury outcomes (PMID:37531413, PMID:36719377).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Identifying the first intracellular signaling partner of CEACAM1 established that it is a substrate and activator of pp60c-src, positioning it as a phosphotyrosine-based signaling receptor rather than a passive adhesion molecule.

    Evidence Co-immunoprecipitation from granulocytes/HT29 cells and in vitro kinase assays with recombinant cytoplasmic domain

    PMID:7478590

    Open questions at the time
    • Identity of the kinase(s) responsible for CEACAM1 phosphorylation in vivo not resolved
    • Functional consequence of Src activation by CEACAM1 not determined
  2. 1999 Medium

    Demonstrating that cross-linking the CEACAM1 N-domain inhibits cytolytic activity of intestinal intraepithelial lymphocytes established that CEACAM1 functions as an inhibitory receptor in the immune system, with domain-level specificity.

    Evidence Expression cloning, Fc fusion binding, and functional cytolysis inhibition assays with iIEL

    PMID:10415036

    Open questions at the time
    • Downstream signaling mechanism of inhibition not identified
    • Whether ITIM phosphatase recruitment mediates the effect was not tested
  3. 2001 High

    Identification of functional ITIMs in the cytoplasmic tail and demonstration that SHP-1/SHP-2 are the required effector phosphatases provided the core molecular mechanism of CEACAM1 inhibitory signaling, while parallel work showed phospho-Tyr488 sequesters Shc to attenuate Ras/MAPK and PI3K/Akt pathways downstream of insulin receptor.

    Evidence FcγRIIB-CEACAM1 chimeras in DT40 B cells with SHP-1/SHP-2-deficient lines and Y459F mutagenesis; GST pull-downs and co-IP in NIH 3T3 cells with MAPK activity rescue

    PMID:11493628 PMID:11694516

    Open questions at the time
    • Whether SHP-1 vs SHP-2 has non-redundant roles in different cell types was unclear
    • Structural basis of ITIM-SHP interaction not determined
  4. 2002 High

    Demonstrating that trans-homophilic CEACAM1 engagement inhibits NK cytotoxicity independently of MHC class I revealed a new immune evasion axis; concurrently, Ser503 phosphorylation was shown to be required for hepatic insulin clearance, establishing CEACAM1 as a metabolic regulator.

    Evidence NK redirected lysis assays with CEACAM1 transfectants; L-SACC1 transgenic mice with S503A mutant metabolic phenotyping

    PMID:11884449 PMID:12128284

    Open questions at the time
    • Molecular link between Ser503 phosphorylation and receptor-mediated endocytosis machinery not identified
    • Ligand on tumor cells engaging CEACAM1 trans-homophilic interaction not fully characterized
  5. 2004 High

    Showing CEACAM1 is an EGFR substrate that sequesters Shc to uncouple EGFR from MAPK signaling unified the Shc-sequestration mechanism across receptor tyrosine kinases, while Tyr488-dependent enhancement of melanoma invasion revealed context-dependent pro-migratory roles.

    Evidence Co-IP in Cos-7/MCF-7 cells plus L-SACC1 transgenic MAPK assays; CEACAM1 transfection in melanoma cells with Y488 mutagenesis and integrin blocking

    PMID:15467833 PMID:15509546

    Open questions at the time
    • How the same Tyr488-Shc interaction mediates growth inhibition in epithelial cells but invasion in melanoma was not reconciled
    • Integrin β3–CEACAM1 crosstalk mechanism not elucidated
  6. 2005 High

    Direct binding of CEACAM1-L to filamin A established a structural link to the actin cytoskeleton, explaining how CEACAM1 reduces cell migration by displacing RalA from filamin A and decreasing focal adhesion turnover.

    Evidence Yeast two-hybrid, SPR, affinity precipitation, and migration/scattering assays in melanoma cells

    PMID:16291724

    Open questions at the time
    • Whether filamin A interaction is regulated by CEACAM1 phosphorylation state was not tested
    • In vivo relevance of the CEACAM1–filamin A complex not demonstrated
  7. 2006 High

    Conditional T cell-specific deletion of CEACAM1 established it as a bona fide T cell inhibitory receptor in vivo, with ITIM-dependent SHP-1 recruitment required for suppression of TCR-CD3 signaling, proliferation, and cytokine production.

    Evidence Conditional KO T cells, in vitro T cell assays, mouse DTH and IBD models, ITIM mutagenesis

    PMID:17081782

    Open questions at the time
    • Relative contributions of SHP-1 vs SHP-2 in T cell inhibition not delineated
    • Whether CEACAM1 inhibitory function is ligand-dependent or constitutive in T cells not resolved
  8. 2008 High

    Bacterial exploitation of CEACAM1 was mechanistically defined: Neisseria/Moraxella Opa/UspA1 engagement triggers ITIM phosphorylation and SHP-1 recruitment to suppress TLR2-NF-κB and PI3K-Akt signaling, while CEACAM1 was separately shown to be an ITIM-dependent inhibitor of platelet GPVI-collagen signaling governing thrombus formation in vivo.

    Evidence Primary pulmonary epithelial infection with bacterial mutants and pathway readouts; Ceacam1−/− platelet aggregation, intravital microscopy, and GPVI depletion rescue

    PMID:18836450 PMID:19008452

    Open questions at the time
    • Whether bacterial engagement activates a distinct downstream program beyond canonical ITIM-SHP1 not known
    • Structural basis of Opa–CEACAM1 N-domain interaction not resolved at atomic level
  9. 2012 High

    Discovery that CEACAM1 forms a ternary complex with TLR4 and phospho-Syk in neutrophils to recruit SHP-1 and suppress inflammasome-driven IL-1β production expanded its inhibitory role to innate immune danger signaling.

    Evidence Co-IP in Ceacam1−/− neutrophils, in vivo bone marrow reconstitution with ITIM-mutant CEACAM1, Syk inhibitors, RNAi

    PMID:22496641

    Open questions at the time
    • Whether CEACAM1 directly interacts with NLRP3 inflammasome components not tested
    • Upstream signal triggering CEACAM1–Syk association not identified
  10. 2013 High

    The NK cell inhibitory mechanism was refined: trans-homophilic CEACAM1 ligation recruits SHP-1 to dephosphorylate Vav1, directly blocking NKG2D cytolytic signaling, identifying a specific phosphatase substrate mediating immune evasion.

    Evidence Co-IP and phospho-Vav1 assays in IL-2-activated mouse and human NK cells plus cytotoxicity assays

    PMID:23696226

    Open questions at the time
    • Whether other activating receptor pathways beyond NKG2D are similarly regulated not tested
    • Structural determinants of CEACAM1–NKG2D co-association not defined
  11. 2014 High

    Structural and functional evidence that CEACAM1 heterodimerizes with TIM-3 via N-terminal IgV domains in both cis and trans, and is required for TIM-3 maturation, surface expression, and inhibitory function, established a new paradigm of immune checkpoint cooperativity; simultaneously, isoform-specific regulation of NKG2D ligand shedding was demonstrated.

    Evidence X-ray crystallography, co-IP, biophysical binding, T cell-specific CEACAM1 KO/reconstitution, adoptive transfer colitis; isoform-specific KD/OE with NK cytotoxicity and xenograft

    PMID:25363763 PMID:25744717

    Open questions at the time
    • Structural basis of cis vs trans dimer selectivity not fully resolved
    • Signaling events downstream of CEACAM1–TIM-3 trans ligation not characterized
  12. 2015 High

    CEACAM1 was shown to promote B cell survival via BTK/Syk/NF-κB signaling and to be required for protective antibody responses during viral infection, establishing a pro-survival function distinct from its canonical inhibitory role.

    Evidence Ceacam1−/− mice, VSV infection, B cell survival flow cytometry, BTK/Syk/NF-κB pathway analysis

    PMID:25692415

    Open questions at the time
    • Whether CEACAM1 directly engages BTK/Syk or acts indirectly not determined
    • Mechanism reconciling pro-survival B cell function with inhibitory signaling in other lymphocytes not established
  13. 2018 High

    CEACAM1 was found to recruit Lck into the immunological synapse of CD8+ T cells, with its absence limiting antiviral T cell activation and antibody-mediated CEACAM1 stabilization preventing exhaustion—revealing a co-stimulatory dimension alongside its inhibitory functions; separately, CEACAM1 was identified as a receptor for H. pylori CagA T4SS injection.

    Evidence LCMV infection in Ceacam1−/− mice, Lck co-IP, synapse imaging, anti-CEACAM1 antibody in mouse/human; CEACAM1 transfection into AZ-521 cells restoring CagA translocation

    PMID:29967450 PMID:30321907

    Open questions at the time
    • How CEACAM1 simultaneously recruits Lck (activating) and SHP-1 (inhibitory) is mechanistically unresolved
    • Whether CagA translocation requires CEACAM1 ITIM signaling not tested
  14. 2019 High

    Fusobacterium nucleatum CbpF was identified as a CEACAM1 ligand that triggers T and NK cell inhibition, extending the bacterial immune evasion paradigm to a tumor-associated pathogen; CEACAM1 was also shown to regulate monocyte IL-6 fever response via SHP-1 sequestration of VAV1 from RP105.

    Evidence F. nucleatum CbpF mutants with CEACAM1 binding/T cell assays; Ceacam1−/− mice LPS challenge with RP105 co-IP

    PMID:30674283 PMID:31069151 PMID:34336716

    Open questions at the time
    • Whether CbpF-CEACAM1 interaction contributes to Fusobacterium-associated colorectal cancer immune evasion in vivo not demonstrated
    • RP105–CEACAM1 interaction awaits structural characterization
  15. 2023 High

    Isoform-specific functions were mechanistically grounded: HIF-1α transcriptionally induces Ptbp1 to splice CEACAM1 toward the short isoform, which protects hepatocytes from ASK1/p-p38 death signaling during hypoxia; conversely, the long isoform in neutrophils restrains NETosis via S1P–S1PR2/3 and autophagy, with its ablation worsening hepatic ischemia-reperfusion injury.

    Evidence ChIP for HIF-1α on Ptbp1 promoter, adenoviral Ceacam1-S reconstitution, morpholino splicing, DMOG treatment; isoform-specific CC1-L ablation in mouse OLT with NETosis/S1P pathway assays and human biopsy validation

    PMID:36719377 PMID:37531413

    Open questions at the time
    • Whether Ptbp1-mediated splicing regulation occurs in non-hepatic tissues not tested
    • Direct molecular target of CEACAM1-S that represses ASK1 not identified
    • How CEACAM1-L regulates S1P receptor balance mechanistically remains unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanism by which CEACAM1 simultaneously mediates inhibitory (SHP-1/SHP-2 recruitment) and activating (Lck recruitment, B cell survival via BTK/Syk) functions in different immune contexts, and how isoform balance is dynamically regulated beyond hepatic ischemia, remain unresolved.
  • No unified model reconciling inhibitory vs co-stimulatory CEACAM1 signaling across cell types
  • Structural basis for isoform-specific partner selectivity not determined
  • In vivo therapeutic window for checkpoint blockade of CEACAM1 vs CEACAM1–TIM-3 axis not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0001618 virus receptor activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-109582 Hemostasis 1
Partners
CEACAM6FLNALCKSHC1SHP-1SHP-2SRCTIM-3
Complex memberships
CEACAM1–TIM-3 heterodimerCEACAM1–TLR4–Syk complexCEACAM1–filamin A complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CEACAM1 forms a heterodimer with TIM-3 via their membrane-distal IgV-like N-terminal domains, both in cis (facilitating TIM-3 maturation and cell surface expression) and in trans (mediating inhibitory signaling); CEACAM1 is required for TIM-3 inhibitory function in T cells Biochemical co-immunoprecipitation, biophysical binding assays, X-ray crystallography, mouse adoptive transfer colitis model, T cell-specific CEACAM1 deletion/reconstitution Nature High 25363763
2006 CEACAM1 isoforms with long cytoplasmic domain inhibit T cell activation (proliferation, cytokine production, allogeneic reactivity) through ITIMs in the cytoplasmic domain that recruit SHP1; conditional T cell deletion of CEACAM1 enhances TCR-CD3 signaling CEACAM1 overexpression and conditional deletion in T cells, in vitro T cell assays, mouse models of delayed-type hypersensitivity and inflammatory bowel disease, ITIM mutagenesis Immunity High 17081782
1995 The cytoplasmic domain of CEACAM1 associates with pp60c-src; the recombinant cytoplasmic domain is both a substrate and binding partner of pp60c-src in vitro, and tyrosine-containing phosphopeptides from the cytoplasmic domain activate pp60c-src kinase activity Co-immunoprecipitation from granulocytes and HT29 cells, in vitro kinase assay with recombinant cytoplasmic domain Oncogene High 7478590
2001 Phosphorylated Tyr488 of CEACAM1 binds the SH2 domain of Shc, sequestering Shc from the insulin receptor/Grb2 complex and down-regulating the Ras/MAP kinase mitogenesis pathway and PI3K/Akt pathway Co-immunoprecipitation in NIH 3T3 cells, GST pull-down assays, Shc SH2 domain overexpression rescue experiments, MAP kinase activity assays The Journal of biological chemistry High 11694516
2002 CEACAM1 regulates insulin clearance in liver; phosphorylation of CEACAM1 on Ser503 is required for receptor-mediated insulin endocytosis and degradation; dominant-negative S503A mutant transgenic mice show impaired insulin clearance and insulin resistance Transgenic mouse overexpressing phosphorylation-defective S503A CEACAM1 mutant in liver (L-SACC1 model), metabolic phenotyping Trends in endocrinology and metabolism: TEM High 12128284
2001 The cytoplasmic tail of CEACAM1 (BGPa) contains functional ITIMs; tyrosine Y459 within the ITIM is required for inhibitory signaling; CEACAM1 inhibitory signaling requires SHP-1 and SHP-2 phosphatases FcγRIIB-BGPa chimeric receptor expressed in DT40 B cells, calcium influx assays, Y459F mutagenesis, SHP-1/SHP-2 mutant DT40 cells Journal of leukocyte biology High 11493628
2008 Bacterial engagement of CEACAM1 (via M. catarrhalis UspA1 or N. meningitidis Opa proteins) triggers tyrosine phosphorylation of CEACAM1 ITIMs, recruits SHP-1, and inhibits TLR2-initiated NF-κB signaling and PI3K-Akt pathway in pulmonary epithelial cells Bacterial infection of primary pulmonary epithelial cells, phosphorylation assays, SHP-1 recruitment assays, NF-κB and Akt pathway readouts Nature immunology High 18836450
2012 LPS-activated neutrophils form a complex of TLR4, phospho-Syk, and phospho-CEACAM1; this complex recruits SHP-1 via CEACAM1 ITIMs to inhibit IL-1β production by the inflammasome; ITIM mutation abolishes this regulation Co-immunoprecipitation, Ceacam1−/− neutrophils, in vivo bone marrow reconstitution with ITIM-mutant CEACAM1, Syk inhibitors, RNAi knockdown PLoS pathogens High 22496641
2013 CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolysis via trans-homophilic CEACAM1 interactions; co-engagement of NKG2D and CEACAM1 causes biochemical association of these receptors and CEACAM1-recruited SHP-1 dephosphorylates Vav1, blocking downstream cytolytic signaling NK cell cytotoxicity assays, co-immunoprecipitation, phosphorylation assays for Vav1, mouse and human NK cells with IL-2-induced CEACAM1 expression European journal of immunology High 23696226
2004 CEACAM1 is a substrate of EGFR; upon phosphorylation, CEACAM1 reduces EGFR-mediated cell growth by binding to and sequestering Shc, uncoupling EGFR from the Ras/MAPK pathway Co-immunoprecipitation in transfected Cos-7 and MCF-7 cells, transgenic L-SACC1 mice with phosphorylation-defective CEACAM1 mutant, MAPK activity assays The Journal of clinical investigation High 15467833
2005 CEACAM1-L cytoplasmic domain directly binds filamin A; when co-expressed, CEACAM1-L and filamin A drastically reduce cell migration and scattering compared with either protein alone; this interaction reduces RalA binding to filamin A and decreases focal adhesion turnover Yeast two-hybrid screen, surface plasmon resonance, affinity precipitation, migration/scattering assays in melanoma cells, focal adhesion assays Journal of cell science High 16291724
2005 CEACAM1-mediated delay of spontaneous and Fas ligand-induced granulocyte apoptosis requires tyrosine phosphorylation of CEACAM1-L, its association with SHP-1, and activation of Erk1/2; caspase-3 is also involved DNA fragmentation assays, annexin V staining, CEACAM1-Fc constructs, CEACAM1-specific Fab fragments, co-immunoprecipitation, kinase activation assays in rat granulocytes European journal of immunology Medium 15909305
2002 Homotypic CEACAM1 interactions between melanoma cells and NK cells provide MHC class I-independent inhibition of NK cytotoxicity; inhibitory strength correlates with CEACAM1 expression levels NK cell cytotoxicity assays, redirected lysis experiments, CD66a transfectants of 721.221 cells, NK clones from melanoma patients Journal of immunology High 11884449
2011 Tumor cell-associated CEACAM1 causes intracellular retention of NKG2D ligands in mouse and human tumor cells; CEACAM1-silenced tumor cells display more cell surface NKG2D ligands and greater sensitivity to NK cell-mediated cytolysis in vitro and rejection in vivo CEACAM1 silencing in tumor cells, flow cytometry for NKG2D ligand surface expression, NK cytotoxicity assays, in vivo tumor rejection The Journal of experimental medicine High 22143889
2018 CEACAM1 is required for recruiting Lck into the TCR complex to form an efficient immunological synapse in CD8+ T cells; absence of CEACAM1 limits antiviral CD8+ T cell activation; anti-CEACAM1 antibody stabilizes Lck in the immunological synapse and prevents CD8+ T cell exhaustion LCMV infection model in Ceacam1−/− mice, immunological synapse imaging, Lck co-immunoprecipitation, anti-CEACAM1 antibody treatment, human virus-specific CD8+ T cell proliferation assay Nature communications High 29967450
2015 CEACAM1 promotes B cell survival via the BTK/Syk/NF-κB signaling axis; Ceacam1−/− mice have reduced B cell survival and fail to mount protective neutralizing antibody responses during cytopathic viral infection Ceacam1−/− mice, VSV infection model, flow cytometry for B cell survival, BTK/Syk/NF-κB pathway analysis Nature communications High 25692415
2004 CEACAM1 expression enhances melanoma cell invasion and migration in a manner dependent on Tyr-488 in the cytoplasmic domain and on αvβ3 integrin; integrin β3 induces CEACAM1 upregulation in melanocytic cells Stable CEACAM1 transfection in melanocytic/melanoma cells, invasion/migration assays, anti-CEACAM antibody blockade, RGD peptide inhibition, Tyr-488 mutagenesis The American journal of pathology High 15509546
2008 CEACAM1 negatively regulates platelet-collagen interactions via GPVI/FcR-γ-chain signaling; Ceacam1−/− platelets show enhanced collagen-mediated aggregation and granule secretion; SHP-1 recruitment through CEACAM1 ITIMs mediates this inhibitory function; ceacam1−/− mice form larger, more stable thrombi in vivo Ceacam1−/− mice, platelet aggregation assays, CRP-stimulation, intravital microscopy of FeCl3-injured mesenteric arterioles, GPVI depletion rescue, pulmonary thromboembolism model Blood High 19008452
2014 CEACAM1 long isoform (CEACAM1-4L) downregulates cell surface NKG2D ligands (MICA, ULBP2) by enhanced shedding, promoting immune escape; whereas CEACAM1-3S isoform upregulates NKG2D ligands and sensitizes melanoma cells to NK lysis — demonstrating isoform-specific immunomodulatory mechanisms Isoform-specific knockdown and overexpression in melanoma cells, flow cytometry for NKG2D ligand surface expression, NK cytotoxicity assays, in vivo xenograft model, patient survival analysis Cancer research Medium 25744717
2019 Fusobacterium nucleatum binds and activates CEACAM1 via its surface protein CbpF (trimeric autotransporter adhesin), leading to inhibition of T and NK cell activities; CbpF-specific mutants abolish CEACAM1 binding and T cell inhibition F. nucleatum mutants lacking CbpF and other trimeric autotransporter adhesins, CEACAM1 binding assays, functional T cell and NK cell inhibition assays, anti-CEACAM1 N-domain antibody blocking Oncoimmunology / Frontiers in cellular and infection microbiology High 31069151 34336716
2005 DC-SIGN binds CEACAM1 on neutrophils via Lewis x glycan moieties specifically expressed on neutrophil-derived CEACAM1; both DC-SIGN-CEACAM1 and DC-SIGN-Mac-1 interactions are required to establish DC-neutrophil cellular contact CEACAM1 binding assays with DC-SIGN, fucosidase treatment, antibody blocking, co-culture DC-neutrophil interaction assays FEBS letters Medium 16246332
2004 CEACAM1 N-glycans from human granulocytes carry Lewis x epitopes; MALDI-TOF MS and sequential exoglycosidase digestion characterized multiple Lewis x glycan structures with alpha(1-3,4) fucose linkages on CEACAM1 Immunoaffinity purification of CEACAM1, Lewis x-specific antibody binding, fucosidase III treatment, MALDI-TOF MS with sequential exoglycosidase digestion Glycobiology High 15317738
2014 CEACAM1 long isoform increases melanoma cell proliferation via upregulation of Sox-2; this effect requires the full-length long cytoplasmic tail and is not reversed by CEACAM1-blocking antibody, indicating it is not mediated by homophilic interactions CEACAM1 knockdown and overexpression of selective variants/truncation mutants, in vitro and in vivo proliferation assays, Sox-2 expression analysis, CEACAM1-blocking antibody treatment Neoplasia Medium 24931667
2019 CEACAM6 expressed on cancer cells inhibits T cell antitumor activity by binding CEACAM1 on activated T cells (trans heterophilic interaction); blocking CEACAM6 with antibody BAY 1834942 reactivates T cell responses Co-culture experiments with T cells and solid cancer cells, CEACAM6-CEACAM1 interaction assays, cytokine and killing assays, comparison with PD-1/PD-L1/TIM-3 checkpoint blockade Oncoimmunology Medium 35141051
2002 CEACAM1 clustering by surface ligation induces rapid tyrosine dephosphorylation, reduced association with SHP2, translocation to actin cytoskeleton, and activation of ERK1/2 MAPK in PC12 cells Antibody-induced CEACAM1 clustering, phosphorylation assays, co-immunoprecipitation with SHP2, detergent fractionation for cytoskeleton association, ERK1/2 activation assay Biological chemistry Medium 12108545
2014 Soluble CEACAM8 binds CEACAM1 on pulmonary epithelial cells and inhibits TLR2-dependent NF-κB signaling via CEACAM1 ITIM phosphorylation and SHP-1 recruitment, suppressing PI3K-Akt pathway activation Recombinant CEACAM8-Fc binding to CEACAM1-positive epithelial cells, TLR2 stimulation assays, ITIM phosphorylation assays, SHP-1 co-immunoprecipitation, Akt pathway readouts PloS one Medium 24743304
2019 CEACAM1 regulates the LPS-driven IL-6 fever response through monocyte RP105 receptor signaling; CEACAM1 recruits SHP-1 to sequester phospho-VAV1 and β-actin from RP105, negatively regulating this pathway; Ceacam1−/− mice over-produce IL-6 in response to LPS Ceacam1−/− mice LPS challenge, in vitro monocyte stimulation, RP105 complex co-immunoprecipitation, SHP-1 recruitment assays, PET imaging with 64Cu-LPS BMC immunology Medium 30674283
2023 HIF-1α controls alternative splicing of CEACAM1 toward the short cytoplasmic isoform (Ceacam1-S) through transcriptional regulation of the Ptbp1 promoter; Ceacam1-S protects hepatocytes from hypoxia-induced loss of adhesion by repressing the ASK1/p-p38 cell death pathway Chromatin immunoprecipitation assays identifying HIF-1α binding to Ptbp1 promoter, luciferase reporter assays, adenoviral Ceacam1-S transfection in KO hepatocytes, morpholino-induced Ceacam1-S splicing, DMOG prolyl hydroxylase inhibitor treatment, in vitro and in vivo mouse models Science translational medicine High 37531413
2023 The long cytoplasmic isoform of CEACAM1 (CC1-L) in neutrophils determines susceptibility to NETosis by regulating the S1P-S1PR2/S1PR3 axis and autophagy signaling; ablation of CC1-L aggravates hepatic ischemia-reperfusion injury by promoting NET formation Mouse OLT model with isoform-specific CC1-L ablation, NETosis assays, S1P-S1PR2/S1PR3 axis analysis, autophagy signaling assays, human liver transplant biopsy analysis The Journal of clinical investigation High 36719377
1999 CD66a (CEACAM1) and CD66b are the major galectin-3 receptors on human neutrophils; both proteins are stored in gelatinase and specific granules and mobilized to the cell surface upon activation Galectin-3-Sepharose affinity chromatography of neutrophil granule proteins, immunoblotting, lactose elution, subcellular fractionation, differentiated HL-60 cells lacking specific granules Journal of immunology Medium 10553088
2018 CEACAM1 expression in hepatocytes protects against ischemia-reperfusion injury by suppressing ASK1/p-p38 upregulation, reducing ROS induction and HMGB1 translocation; CC1-deficient livers show augmented cold stress-triggered ASK1/p-p38 signaling CC1-KO mouse OLT model, ASK1 inhibition rescue, ROS and HMGB1 assays, bone marrow-derived macrophage co-culture, siRNA ASK1 silencing in hepatocyte cultures, human liver biopsy correlation The Journal of clinical investigation High 32027621
2018 CEACAM1 deficiency causes eNOS depalmitoylation and subcellular redistribution, altered endothelial glycocalyx (through repression of glycocalyx-degrading enzymes), increased leukocyte-endothelial adhesion, and age-dependent modulation of endothelial barrier function through β-catenin and caveolin-1 phosphorylation Ceacam1−/− mice, eNOS localization by immunofluorescence, glycocalyx assays, leukocyte adhesion assays, β-catenin/caveolin-1 phosphorylation Western blot, TNF-α stimulation FASEB journal Medium 29746166
2015 Forced hepatic CEACAM1 overexpression in mice prevents high-fat diet-induced hyperinsulinemia, insulin resistance, and hepatic lipid accumulation partly by increasing hepatic β-fatty acid oxidation and energy expenditure Liver-specific inducible CEACAM1 expression (L-CC1) transgenic mice, high-fat diet metabolic challenge, glucose/insulin tolerance tests, fatty acid oxidation assays Diabetes High 25972571
2018 CEACAM1 or CEACAM5 expression in AZ-521 cells (which lack CEACAMs) restores H. pylori type IV secretion system-mediated CagA translocation and phosphorylation, identifying CEACAM1 as a T4SS receptor for CagA injection CEACAM1/CEACAM5/CEACAM6 transfection into AZ-521 cells, H. pylori infection, CagA translocation and phosphorylation assays, vinculin/cortactin dephosphorylation assays Cellular microbiology High 30321907
1999 Cross-linking of CEACAM1 on intestinal intraepithelial lymphocytes (iIEL) with mAbs recognizing the N domain inhibits anti-CD3-directed and LAK cytolytic activity; the N domain mediates inhibitory signaling Expression cloning identifying CEACAM1 as mAb antigen, Fc fusion protein binding studies, functional cytolysis inhibition assays with iIEL Journal of immunology Medium 10415036

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 583 25363763
1996 CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 169 8543780
2002 CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 145 11884449
2019 Fusobacterium nucleatum supresses anti-tumor immunity by activating CEACAM1. Oncoimmunology 134 31069151
1996 CD66a, CD66b, CD66c, and CD66d each independently stimulate neutrophils. Journal of leukocyte biology 120 8699114
2006 SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms. Immunity 117 17081782
1995 Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion molecule of the carcinoembryonic antigen family downregulated in colorectal carcinomas. Oncogene 114 7478590
2002 Regulation of insulin action by CEACAM1. Trends in endocrinology and metabolism: TEM 106 12128284
2004 CEACAM1 enhances invasion and migration of melanocytic and melanoma cells. The American journal of pathology 104 15509546
2020 EpCAM-high liver cancer stem cells resist natural killer cell-mediated cytotoxicity by upregulating CEACAM1. Journal for immunotherapy of cancer 103 32221015
2008 CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells. Nature immunology 101 18836450
2021 Mitochondria-targeted therapeutics, MitoQ and BGP-15, reverse aging-associated meiotic spindle defects in mouse and human oocytes. Human reproduction (Oxford, England) 100 33367783
2019 CEACAM1 structure and function in immunity and its therapeutic implications. Seminars in immunology 93 31604530
1999 Identification of CD66a and CD66b as the major galectin-3 receptor candidates in human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 92 10553088
2014 The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice. Nature communications 91 25489988
2005 Interactions of DC-SIGN with Mac-1 and CEACAM1 regulate contact between dendritic cells and neutrophils. FEBS letters 79 16246332
1999 Regulation of human intestinal intraepithelial lymphocyte cytolytic function by biliary glycoprotein (CD66a). Journal of immunology (Baltimore, Md. : 1950) 79 10415036
1998 Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer. The American journal of pathology 78 9626043
2005 CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes. European journal of immunology 74 15909305
1999 Tumor-suppressive activity of CD66a in prostate cancer. Cancer gene therapy 74 10419049
2012 CEACAM1 negatively regulates IL-1β production in LPS activated neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex. PLoS pathogens 72 22496641
2001 Biliary glycoprotein (BGPa, CD66a, CEACAM1) mediates inhibitory signals. Journal of leukocyte biology 66 11493628
2011 Re-expression of CEACAM1 long cytoplasmic domain isoform is associated with invasion and migration of colorectal cancer. International journal of cancer 64 21413011
2008 CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo. Blood 64 19008452
2005 Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production. Infection and immunity 64 15972507
2011 CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells. The Journal of experimental medicine 60 22143889
2001 Shc and CEACAM1 interact to regulate the mitogenic action of insulin. The Journal of biological chemistry 58 11694516
1998 Expression of biliary glycoprotein (CD66a) in normal and malignant breast epithelial cells. Anticancer research 58 9858884
2004 CEACAM1 modulates epidermal growth factor receptor--mediated cell proliferation. The Journal of clinical investigation 57 15467833
2003 CEACAM1 is a potent regulator of B cell receptor complex-induced activation. Journal of leukocyte biology 56 12832451
2009 BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury. Toxicology and applied pharmacology 55 19931551
2006 Bgp, a secreted glycosaminoglycan-binding protein of Borrelia burgdorferi strain N40, displays nucleosidase activity and is not essential for infection of immunodeficient mice. Infection and immunity 54 16622242
2021 Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation. Frontiers in cellular and infection microbiology 52 34336716
2015 Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance. Diabetes 52 25972571
1990 Properties of BGP1, a poly(dG)-binding protein from chicken erythrocytes. Nucleic acids research 52 2402439
2020 Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury. The Journal of clinical investigation 51 32027621
2012 BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Molecular and cellular biochemistry 49 22350755
2019 Fusobacterium spp. target human CEACAM1 via the trimeric autotransporter adhesin CbpF. Journal of oral microbiology 48 30719234
2018 CEACAM1 in Liver Injury, Metabolic and Immune Regulation. International journal of molecular sciences 48 30314283
2014 Soluble CEACAM8 interacts with CEACAM1 inhibiting TLR2-triggered immune responses. PloS one 48 24743304
2013 CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. European journal of immunology 48 23696226
2011 The CEACAM1 expression is decreased in the liver of severely obese patients with or without diabetes. Diagnostic pathology 47 21569294
2018 CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection. Nature communications 46 29967450
2000 The adhesion molecule CEACAM1 (CD66a, C-CAM, BGP) is specifically expressed by the extravillous intermediate trophoblast. The American journal of pathology 46 10751340
2004 Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical malformation. Neurology 45 15159468
2000 Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell response. European journal of immunology 45 11009093
2006 Role of CEACAM1 as a regulator of T cells. Annals of the New York Academy of Sciences 44 17057197
1994 CD66 identifies the biliary glycoprotein (BGP) adhesion molecule: cloning, expression, and adhesion functions of the BGPc splice variant. Blood 44 8018919
2015 CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production. Nature communications 43 25692415
2004 The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma. The Journal of pathology 43 15476270
2023 Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation. The Journal of clinical investigation 42 36719377
2005 CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration. Journal of cell science 42 16291724
2004 Identification of Lewis x structures of the cell adhesion molecule CEACAM1 from human granulocytes. Glycobiology 40 15317738
2024 BGP-15 alleviates LPS-induced depression-like behavior by promoting mitophagy. Brain, behavior, and immunity 36 38677623
2021 T cell-mediated elimination of cancer cells by blocking CEACAM6-CEACAM1 interaction. Oncoimmunology 36 35141051
2013 CEACAM1 loss links inflammation to insulin resistance in obesity and non-alcoholic steatohepatitis (NASH). Seminars in immunopathology 36 24258517
2019 Size Matters: The Functional Role of the CEACAM1 Isoform Signature and Its Impact for NK Cell-Mediated Killing in Melanoma. Cancers 35 30871206
2018 Expression of CEACAM1 or CEACAM5 in AZ-521 cells restores the type IV secretion deficiency for translocation of CagA by Helicobacter pylori. Cellular microbiology 35 30321907
2010 Generation of human CEACAM1 transgenic mice and binding of Neisseria Opa protein to their neutrophils. PloS one 35 20404914
2014 CEACAM1 promotes melanoma cell growth through Sox-2. Neoplasia (New York, N.Y.) 33 24931667
2018 On the Dual Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1) in Human Malignancies. Journal of immunology research 32 30406153
2016 The role of CEA-related cell adhesion molecule-1 (CEACAM1) in vascular homeostasis. Histochemistry and cell biology 32 27695943
2004 Biological function of the soluble CEACAM1 protein and implications in TAP2-deficient patients. European journal of immunology 32 15259011
2022 TIM3/CEACAM1 pathway involves in myeloid-derived suppressor cells induced CD8+ T cells exhaustion and bone marrow inflammatory microenvironment in myelodysplastic syndrome. Immunology 31 35470423
2018 Endothelial barrier function is differentially regulated by CEACAM1-mediated signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 31 29746166
2017 Loss of Hepatic CEACAM1: A Unifying Mechanism Linking Insulin Resistance to Obesity and Non-Alcoholic Fatty Liver Disease. Frontiers in endocrinology 31 28184213
1997 Dysregulation of carcinoembryonic antigen group members CGM2, CD66a (biliary glycoprotein), and nonspecific cross-reacting antigen in colorectal carcinomas. Comparative analysis by northern blot and in situ hybridization. The American journal of pathology 31 9250164
1993 Serum levels of bone Gla protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegaly: effects of long-term octreotide treatment. Calcified tissue international 30 8481830
2012 The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics. Cell stress & chaperones 29 22322357
1989 Bone GLA protein (BGP) levels and bone turnover in rheumatoid arthritis. British journal of rheumatology 29 2786438
2016 SOX9 indirectly regulates CEACAM1 expression and immune resistance in melanoma cells. Oncotarget 28 26885752
2020 TIM-3 and CEACAM1 do not interact in cis and in trans. European journal of immunology 27 32222966
2019 CEACAM1 regulates the IL-6 mediated fever response to LPS through the RP105 receptor in murine monocytes. BMC immunology 26 30674283
2004 Extracellular secretion of the Borrelia burgdorferi Oms28 porin and Bgp, a glycosaminoglycan binding protein. Infection and immunity 26 15501754
2015 CEACAM1-3S Drives Melanoma Cells into NK Cell-Mediated Cytolysis and Enhances Patient Survival. Cancer research 25 25744717
2018 CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells. Scientific reports 24 30089785
1990 Influence of sex, age, and menopause in serum osteocalcin (BGP) levels. Klinische Wochenschrift 24 2135297
2022 A Selective β-Catenin-Metadherin/CEACAM1-CCL3 Axis Mediates Metastatic Heterogeneity upon Tumor-Macrophage Interaction. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 35403834
2023 Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans. Science translational medicine 22 37531413
2021 BGP-15 Protects against Heart Failure by Enhanced Mitochondrial Biogenesis and Decreased Fibrotic Remodelling in Spontaneously Hypertensive Rats. Oxidative medicine and cellular longevity 21 33564362
2018 Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 29486474
2015 Down-regulation of CEACAM1 in breast cancer. Acta biochimica et biophysica Sinica 21 26341981
2012 CEACAM1 in malignant melanoma: a diagnostic and therapeutic target. Current topics in medicinal chemistry 21 22196267
1995 CD49f (alpha 6 integrin) and CD66a (BGP) are specifically induced by retinoids during human monocytic differentiation. Leukemia 21 8609714
2010 Regulation of CEACAM1 transcription in human breast epithelial cells. BMC molecular biology 20 21050451
2015 Hepatic CEACAM1 Over-Expression Protects Against Diet-Induced Fibrosis and Inflammation in White Adipose Tissue. Frontiers in endocrinology 18 26284027
1991 Serum bone Gla protein (BGP) during treatment of hyperthyroidism and hypothyroidism. A longitudinal study. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 1864560
1990 Measurement of serum bone gla-protein (BGP) in humans with an ovine BGP-based radioimmunoassay. Clinical chemistry 18 2208702
2008 Cytokine-induced CEACAM1 expression on keratinocytes is characteristic for psoriatic skin and contributes to a prolonged lifespan of neutrophils. The Journal of investigative dermatology 17 18843289
2007 Heparan sulfate is a binding molecule but not a receptor for CEACAM1-independent infection of murine coronavirus. Virology 17 17692355
2018 BGP: identifying gene-specific branching dynamics from single-cell data with a branching Gaussian process. Genome biology 16 29843817
2009 Expression of newly identified secretory CEACAM1(a) isoforms in the intestinal epithelium. Biochemical and biophysical research communications 16 19358828
2002 Secreted CEACAM1 splice variants in rat cell lines and in vivo in rat serum. Biochemical and biophysical research communications 16 11922629
2023 T Cell CEACAM1-TIM-3 Crosstalk Alleviates Liver Transplant Injury in Mice and Humans. Gastroenterology 15 37479191
2022 Identification of BgP, a Cutinase-Like Polyesterase From a Deep-Sea Sponge-Derived Actinobacterium. Frontiers in microbiology 15 35495686
2018 The Borrelia burgdorferi Glycosaminoglycan Binding Protein Bgp in the B31 Strain Is Not Essential for Infectivity despite Facilitating Adherence and Tissue Colonization. Infection and immunity 15 29158428
2018 Assessing the Impact of Targeting CEACAM1 in Head and Neck Squamous Cell Carcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 15 29436278
2016 CEACAM1 is overexpressed in oral tumors and related to tumorigenesis. Medical molecular morphology 15 27464654
2004 Retinoic acid treated HL60 cells express CEACAM1 (CD66a) and phagocytose Neisseria gonorrhoeae. FEMS immunology and medical microbiology 15 15364113
2002 Clustering-induced signaling of CEACAM1 in PC12 cells. Biological chemistry 15 12108545