Affinage

CEACAM6

Cell adhesion molecule CEACAM6 · UniProt P40199

Length
344 aa
Mass
37.2 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEACAM6 is a GPI-anchored, heavily N-glycosylated immunoglobulin-superfamily cell-surface glycoprotein that mediates Ca2+-independent homophilic (CEACAM6-CEACAM6) and heterophilic (CEACAM6-CEA, CEACAM6-CEACAM8/CD66b) adhesion through its N-terminal Ig-like domain (PMID:2803308, PMID:2830274, PMID:2022629, PMID:11590190). The mature protein carries an N-terminal domain plus a single Ig-like doublet and is attached to the membrane via an amide-linked GPI anchor at residue ~287, removable by PI-specific phospholipase C (PMID:2742579, PMID:3390172, PMID:2830274). In neutrophils it is stored in secondary granules as a surface-recruitable pool, carries selectin-binding Lewis-X/sialyl-Lewis-X glycans, and transduces an extracellular-calcium-dependent activation signal that upregulates CD11/CD18 and promotes endothelial adhesion and superoxide release (PMID:1640165, PMID:7689841, PMID:8699114, PMID:8645267). In epithelial cancers, CEACAM6 cross-linking or homophilic engagement drives a caveolin-1- and c-Src-dependent signaling cascade that phosphorylates FAK and Akt to confer anoikis resistance, invasion, proliferation, EMT, and metastasis; downstream effectors include MMP-9/MMP-2, cyclin D1/CDK4, and PI3K/AKT, and CEACAM6 cooperates with integrins and IGF-IR in this output (PMID:15047698, PMID:14724575, PMID:15316565, PMID:15208677, PMID:25398131, PMID:26497080). It physically co-clusters with integrin α5β1 to enhance fibronectin binding and matrix assembly, and engages EGFR in an N-glycosylation (Asn256/MGAT5)-dependent manner to amplify EGFR signaling and invasion (PMID:17167768, PMID:28892050). CEACAM6 expression is controlled by TGF-β/Smad3 and by HIF-1 binding to hypoxia-responsive elements whose CpG methylation status sets expression level, and it is post-transcriptionally repressed by miR-29 and miR-146a/miR-26a (PMID:17653079, PMID:24898815, PMID:23857344, PMID:32648688). At mucosal surfaces it serves as an apical epithelial receptor for type-1-pili and long-polar-fimbriae adherent-invasive E. coli, mediating colonization and transepithelial translocation in a manner inducible by IFN-γ/TNF-α (PMID:17525800, PMID:31393983). CEACAM6 also functions as an immune checkpoint by binding CEACAM1 on activated T cells to suppress anti-tumor immunity (PMID:35141051).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1988 High

    Defining the primary structure and domain architecture established CEACAM6 as a CEA-related Ig-superfamily glycoprotein, distinguishing it from CEA by a single Ig doublet and a C-terminal membrane-anchoring domain.

    Evidence cDNA cloning/sequencing from colon carcinoma SW403 and amino-acid sequencing of purified NCA-50 protein

    PMID:2830274 PMID:3390172

    Open questions at the time
    • No 3D structure of the N-domain at the time
    • Function not yet assigned
  2. 1989 High

    Reconstitution in transfected cells showed CEACAM6 is a functional adhesion molecule and that it is GPI-anchored, defining both its activity and its membrane attachment mode.

    Evidence CHO/NIH-3T3 transfection with cell aggregation and 51Cr adhesion assays, Fab' inhibition, and PI-PLC release with flow cytometry

    PMID:2742579 PMID:2803308

    Open questions at the time
    • Adhesion partners beyond homophilic/CEA not yet mapped
    • No cytoplasmic signaling output (GPI-anchored, lacks intracellular domain)
  3. 1991 High

    Domain-mapping localized adhesion specificity to the N-terminal domain, identifying the binding surface that mediates both homophilic and heterophilic engagement.

    Evidence Chimeric and N-domain-substituted constructs in CHO adhesion assays

    PMID:2022629

    Open questions at the time
    • Atomic-resolution binding interface unresolved
  4. 1996 High

    Work in neutrophils showed CEACAM6 transmits an activation signal despite being GPI-anchored, and that heterophilic CD66c-CD66b binding is carbohydrate-independent, separating protein-protein adhesion from glycan-mediated functions.

    Evidence Anti-CD66c antibody stimulation with calcium chelation and CD18 blocking; recombinant deglycosylated proteins in adhesion and superoxide assays

    PMID:8645267 PMID:8699114

    Open questions at the time
    • Signal transducer coupling a GPI protein to intracellular response not identified
    • Specific glycan determinants of selectin binding not mapped
  5. 2001 High

    Systematic mutagenesis defined the overlapping residues controlling homophilic, CEACAM8-heterophilic, and bacterial Opa binding, establishing a shared but distinguishable adhesion surface.

    Evidence Homologue-scanning mutagenesis of CHO transfectants in adhesion assays

    PMID:11590190

    Open questions at the time
    • Structural basis for partner selectivity unresolved
  6. 2004 High

    A series of pancreatic-cancer studies placed CEACAM6 atop a caveolin-1/c-Src/FAK/Akt signaling axis controlling anoikis resistance, invasion, MMP activity, IGF-IR upregulation, and in vivo metastasis, transforming it from an adhesion molecule into an oncogenic signaling hub.

    Evidence Antibody cross-linking, siRNA/overexpression, dominant-negative/constitutively-active c-Src and caveolin-1, anoikis/invasion assays, orthotopic xenografts

    PMID:14724575 PMID:15047158 PMID:15047698 PMID:15208677 PMID:15316565

    Open questions at the time
    • How a GPI-anchored protein couples to c-Src not mechanistically resolved
    • Direct kinase activation step undefined
  7. 2007 High

    CEACAM6 was shown to co-cluster with integrin α5β1 to drive fibronectin matrix assembly and to be transcriptionally controlled by TGF-β/Smad3, linking its adhesion function to ECM remodeling and upstream regulation.

    Evidence Confocal co-clustering, fibronectin assembly and blocking assays; promoter-luciferase reporter and Smad3-null mouse analysis

    PMID:17167768 PMID:17653079

    Open questions at the time
    • Stoichiometry/physical nature of CEACAM6-integrin complex undefined
    • Other transcriptional inputs not surveyed
  8. 2007 High

    Identification of CEACAM6 as the apical ileal-epithelial receptor for type-1-pili AIEC, inducible by inflammatory cytokines, established its role in pathogenic bacterial colonization in Crohn's disease.

    Evidence Primary enterocyte adhesion with pili-mutant bacteria, antibody blocking, cytokine stimulation, immunohistochemistry

    PMID:17525800

    Open questions at the time
    • Bacterial ligand-CEACAM6 binding interface not mapped at residue level
    • Downstream epithelial response to AIEC binding incomplete
  9. 2014 High

    Epigenetic mapping showed HIF-1/HRE methylation status governs CEACAM6 expression, with a humanized transgenic mouse linking diet-induced HRE demethylation to enhanced AIEC colonization, defining an environmental-epigenetic control loop.

    Evidence Bisulfite/SnapShot methylation analysis, pCpGfree reporter, human-CEACAM6 transgenic mice on low-methyl diet, colonization quantification

    PMID:24898815

    Open questions at the time
    • Enzymes setting/removing HRE methylation not identified
    • Generalizability beyond intestine untested
  10. 2017 High

    CEACAM6 was shown to physically engage EGFR in an Asn256/MGAT5-glycosylation-dependent manner to amplify EGFR signaling and invasion, and separately to act as an immune checkpoint by binding CEACAM1 on T cells, broadening its oncogenic and immune roles.

    Evidence Co-IP of CEACAM6-EGFR, N256 mutagenesis, MGAT5 knockdown; T-cell/cancer co-culture with CEACAM6-blocking antibody and cytokine/killing readouts

    PMID:28892050 PMID:35141051

    Open questions at the time
    • EGFR-CEACAM6 interaction validated in single tumor context
    • CEACAM6-CEACAM1 checkpoint data from single lab co-culture
  11. 2019 High

    CRISPR knockout with quantitative proteomics broadened CEACAM6's functional footprint to catabolism, transmembrane transport, autophagy, and mitochondrial respiration, indicating effects beyond adhesion and Src signaling.

    Evidence CRISPR/Cas9 knockout in HPAF-II, mass-spec proteomics, Seahorse bioenergetics, nude-mouse xenograft

    PMID:31797958

    Open questions at the time
    • Direct molecular links between CEACAM6 and metabolic/autophagy changes unestablished
    • Proteomic associations not mechanistically dissected
  12. 2023 Medium

    Discovery of lysine-lactylation stabilizing CEACAM6 downstream of an ALDOB/PDK1/lactate axis, and of a negative-regulatory role in HO-1 antioxidant defense, extended its regulation to metabolic post-translational control and oxidative-stress biology.

    Evidence Lactylation detection with lactate measurement and PDK1 analysis in CRC cells; AAV overexpression in human precision-cut lung slices with nitrosative-stress readouts

    PMID:37219322 PMID:37816733

    Open questions at the time
    • Lactylation site and its functional consequence on CEACAM6 not mapped
    • HO-1 regulatory mechanism by a surface GPI protein unclear
    • Both from single labs

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a GPI-anchored extracellular protein lacking a cytoplasmic domain physically couples to intracellular c-Src/FAK/Akt signaling, and the atomic-resolution architecture of its N-domain adhesion and EGFR/integrin co-clustering interfaces, remain unresolved.
  • No structural model of N-domain partner complexes
  • Transmembrane coupling mechanism to Src undefined
  • Lipid-raft/caveolin organization not structurally characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0001618 virus receptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CD151CEACAM1CEACAM5CEACAM8EGFRITGA5ITGB1SRC

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CEACAM6 (NCA) expressed on CHO cell surfaces mediates both homophilic (NCA-NCA) and heterophilic (CEA-NCA) Ca2+-independent cell adhesion, as demonstrated by aggregation and 51Cr-labeled cell adhesion assays with Fab' antibody inhibition. CHO cell transfection with cDNA, cell aggregation assay, 51Cr-labeled adhesion assay, Fab' antibody inhibition Biochemical and biophysical research communications High 2803308
1989 CEACAM6 (NCA) is anchored to the cell membrane via a glycosyl-phosphatidylinositol (GPI) linkage, demonstrated by phosphatidylinositol-specific phospholipase C cleavage releasing the protein from NIH/3T3 transfectant surfaces. cDNA transfection of NIH/3T3 cells, PI-PLC treatment, flow cytometry, immunoprecipitation of surface-labeled glycoproteins Biochemical and biophysical research communications High 2742579
1988 CEACAM6 (NCA) protein contains four cysteine residues that form disulfide bonds, has 7 potential N-glycosylation sites with differential occupancy, and is GPI-anchored via an amide linkage to ethanolamine at amino acid position 287 (replacing the last 24 hydrophobic residues of the primary sequence). Amino acid sequencing of purified NCA-50 protein, biochemical characterization Biochemical and biophysical research communications High 3390172
1988 CEACAM6 (NCA) encodes a mature protein of 310 amino acids with one immunoglobulin-like doublet domain (versus three in CEA), an N-terminal domain, and a C-terminal hydrophobic domain sufficient for membrane anchoring; it shares ~85% amino acid homology with CEA. cDNA cloning and sequencing from colon carcinoma cell line SW403 lambda gt10 library The Journal of biological chemistry High 2830274
1991 The heterophilic cell adhesion between CEACAM6 (NCA) and W272 (CGM6/CD67) is mediated specifically by the N-terminal domain of CEACAM6, not by other domains; chimeric N-domain substitution experiments localized the binding specificity to the N-terminal region of the CEACAM6 N-domain. CHO cell transfection with cDNA constructs encoding full-length, chimeric, and N-domain-substituted proteins; cell adhesion assay The Journal of biological chemistry High 2022629
1992 In human neutrophils, CEACAM6 (NCA species of ~95–100 kDa) is predominantly located in secondary granules with lesser amounts in plasma membranes, indicating that secondary granules serve as an intracellular reservoir from which CEACAM6 can be recruited to the cell surface upon activation. Nitrogen cavitation, differential centrifugation subcellular fractionation, SDS-PAGE, immunoblotting Journal of leukocyte biology High 1640165
1993 CEACAM6 (NCA-160, CD66) is the major protein carrier of the selectin-binding carbohydrate groups LewisX and sialyl LewisX on the neutrophil surface, and differently glycosylated forms of CEACAM6 are independently regulated in surface expression following fMLP stimulation. Immunoprecipitation, immunoblotting with carbohydrate-specific antibodies, fMLP stimulation assay Biochemical and biophysical research communications Medium 7689841
1996 Antibody-mediated engagement of CD66c (CEACAM6) on neutrophils independently triggers a transient activation signal requiring extracellular calcium, leading to upregulation of CD11/CD18 and increased neutrophil adhesion to endothelial cells; CD66c can transmit signals independently of CD66a, CD66b, and CD66d. Anti-CD66c antibody stimulation of isolated neutrophils, adhesion assay to HUVEC monolayers, calcium chelation experiments, CD18 blocking antibody, sequential desensitization experiments Journal of leukocyte biology Medium 8699114
1996 Heterophilic adhesion between CD66c (CEACAM6) and CD66b (CGM6) is mediated by interaction between the N-domains of each protein; deglycosylated forms retained adhesion activity, indicating the carbohydrate portions are not required for binding. Activated neutrophils adhering to immobilized CD66b/CD66c released superoxide anions. Recombinant soluble proteins prepared in silkworm larvae, immobilized protein adhesion assay with CHO transfectants, deglycosylation, N-domain-specific antibody inhibition, superoxide anion release assay Biochemical and biophysical research communications High 8645267
2001 The N-domain of CEACAM6 on one cell binds the N-domain of CEACAM6 or CEACAM8 on the opposing cell; homologue-scanning mutagenesis showed that the critical residues for CEACAM6 homophilic and CEACAM6-CEACAM8 heterophilic adhesion overlap and are highly similar but not identical to those required for binding bacterial Opa proteins. CHO transfectants with mutant and chimeric proteins, homologue-scanning mutagenesis, cell adhesion assay Journal of leukocyte biology High 11590190
2004 CEACAM6 cross-linking in pancreatic adenocarcinoma cells activates c-Src and induces tyrosine phosphorylation of FAK (p125FAK); FAK phosphorylation requires c-Src kinase activity, and c-Src activation requires caveolin-1. Cross-linking also increases anchorage-independent survival (anoikis resistance). Antibody-mediated CEACAM6 cross-linking in BxPC3 cells, immunoblotting for pFAK and pSrc, dominant-negative caveolin-1 constructs, anoikis assay The Journal of biological chemistry High 15047698
2004 CEACAM6 cross-linking initiates c-Src-dependent cross-talk between CEACAM6 and αvβ3 integrin, leading to increased pancreatic adenocarcinoma cell adhesion to fibronectin and vitronectin; this was dependent on c-Src activity demonstrated by pharmacological inhibitor PP2 and Src-specific siRNA. Antibody-mediated CEACAM6 cross-linking, cell adhesion assay to ECM proteins, PP2 Src inhibitor, c-Src specific siRNA, integrin-blocking antibodies Biochemical and biophysical research communications High 15047158
2004 CEACAM6 silencing by siRNA in pancreatic adenocarcinoma cells increases susceptibility to caspase-mediated anoikis under anchorage-independent conditions and decreases Akt phosphorylation (Ser-473); CEACAM6 knockdown also reverses acquired anoikis resistance and inhibits in vivo metastatic ability in nude mouse orthotopic xenografts. CEACAM6-specific siRNA, poly-HEMA anoikis induction, YO-PRO-1/PI flow cytometry, fluorometric caspase profiling, Z-VAD-fmk caspase inhibitor, Akt phosphorylation immunoblotting, orthotopic nude mouse xenograft Oncogene High 14724575
2004 CEACAM6 overexpression increases pancreatic adenocarcinoma cellular invasiveness in a c-Src-dependent manner; c-Src-dependent modulation of MMP-9 activity contributes significantly to the increased invasiveness; dominant-negative c-Src blocks invasion while constitutively active c-Src mimics the effect. Stable retroviral CEACAM6 overexpression/RNAi knockdown, modified Boyden chamber invasion assay, constitutively active/dominant-negative c-Src constructs, MMP-9 activity measurement British journal of cancer High 15316565
2004 CEACAM6 overexpression increases IGF-I-induced pancreatic adenocarcinoma invasiveness by upregulating IGF-IR expression and activating both Akt and c-Src kinases; Akt is both necessary and sufficient for IGF-IR upregulation, while c-Src is necessary but insufficient alone; MMP-2 expression and activity are increased in a CEACAM6/IGF-I-dependent manner. Stable CEACAM6 transfection, inhibitory anti-IGF-IR antibody, Akt kinase assay, c-Src kinase assay, MMP-2 zymography, Boyden chamber invasion assay Oncogene High 15208677
2004 CEACAM6 cross-linking induces its cytoplasmic accumulation in pancreatic adenocarcinoma cells; this internalization can be exploited for antibody-mediated delivery of saporin (ribosomal inhibitory protein), inducing caspase-mediated apoptosis in vitro and suppressing tumor growth in vivo. Anti-CEACAM6 antibody cross-linking, immunofluorescence for cytoplasmic accumulation, saporin-conjugated secondary antibody cytotoxicity assay, caspase activation assay, nude mouse xenograft Biochemical and biophysical research communications Medium 15081416
2005 Anti-CEACAM6 antibody Fabs targeting the N-domain (MN-3) and A1B1 domain (MN-15) inhibit tumor cell migration, invasion through ECM, and adhesion to endothelial cells; MN-15 Fab specifically reduces adhesion of some cell lines to fibronectin but not vitronectin, laminin, or collagens; both MN-3 and MN-15 Fabs have antimetastatic effects in vivo improving survival in a colonic micrometastasis model. Migration assay, Matrigel invasion assay, adhesion assay to endothelial cells and ECM proteins, GW-39 colonic micrometastasis nude mouse model, Kaplan-Meier survival analysis Cancer research Medium 16204051
2007 CEACAM6 acts as a receptor for type-1-pili-expressing adherent-invasive E. coli (AIEC) on the apical surface of ileal epithelial cells; AIEC adhesion is dependent on both bacterial type 1 pili expression and CEACAM6 expression on enterocytes; CEACAM6 expression is induced by IFN-γ, TNF-α, and AIEC infection itself, creating a positive-feedback colonization loop. Primary ileal enterocyte adhesion assay, type-1-pili mutant bacteria, anti-CEACAM6 antibody blocking, cytokine stimulation of cultured intestinal epithelial cells, immunohistochemistry The Journal of clinical investigation High 17525800
2007 GPI-anchored CEACAM6 co-clusters with integrin α5β1 on the cell surface and enhances α5β1 binding to fibronectin without changing α5β1 surface levels, leading to increased fibronectin adhesion, enhanced fibronectin matrix assembly, and formation of a polymerized fibronectin 'cocoon'; disruption with anti-fibronectin or anti-α5β1 antibodies restores differentiation and anoikis sensitivity. Confocal microscopy co-clustering, fibronectin-binding assay, fibronectin matrix assembly assay, antibody blocking of fibronectin and α5β1, differentiation and anoikis assays in CEA/CEACAM6-expressing cells Journal of cellular physiology High 17167768
2007 CEACAM6 (and CEACAM5) expression is transcriptionally regulated by the TGF-β signaling pathway via the Smad3 mediator; restoration of TGF-β signaling in Smad3-deficient cells induced CEACAM6 expression and increased CEACAM6 promoter activity; CEACAM6 expression was markedly decreased in Smad3 null mice stomachs. TGF-β treatment of gastric cancer cell lines, Smad3 restoration by transfection, CEACAM6 promoter-luciferase reporter assay, RT-PCR, immunohistochemistry in Smad3 null mice Oncogene High 17653079
2009 CEACAM6 antagonizes the Src signaling pathway, downregulates cancer cell cytoskeleton proteins, and blocks adenovirus trafficking to the nucleus of pancreatic cancer cells; Src-selective inhibitor treatment phenocopied CEACAM6 overexpression in reducing adenovirus replication; siRNA knockdown of CEACAM6 enhanced oncolytic adenovirus antitumor effects in xenografts. CEACAM6 overexpression/siRNA knockdown, adenovirus infection assay, immunofluorescence for viral trafficking, Src inhibitor treatment, cytoskeletal protein immunoblotting, nude mouse xenograft The Journal of clinical investigation Medium 19411761
2012 Influenza A virus neuraminidase (NA) protein physically interacts with CEACAM6 (C6); this NA/CEACAM6 interaction activates the Src/Akt signaling axis, increasing tyrosyl phosphorylation of Src, FAK, Akt, GSK3β, and Bcl-2, enhancing cell survival; siRNA knockdown of CEACAM6 reduced pSrc, pFAK, pAkt, increased apoptosis, and reduced viral protein expression and viral titers. Co-immunoprecipitation (NA-CEACAM6 interaction), CEACAM6 siRNA knockdown, immunoblotting for phosphoproteins, apoptosis assay, viral titer measurement The Journal of biological chemistry Medium 22396546
2013 CEACAM6 promotes EMT in pancreatic cancer cells (increased N-cadherin, vimentin, Slug; decreased E-cadherin); miR-29a/b/c negatively regulates CEACAM6 expression at the post-transcriptional level and suppresses CEACAM6-induced EMT. CEACAM6 overexpression/shRNA knockdown, EMT marker immunoblotting, migration/invasion assays, in vivo metastasis model, miR-29a/b/c transfection International journal of oncology Medium 23857344
2014 CEACAM6 promotes EMT in gastric cancer via activation of PI3K/AKT signaling; overexpressed CEACAM6 increased phosphorylated AKT levels and elevated MMP-9 activity; PI3K inhibitor LY294002 reversed CEACAM6-induced EMT; anti-MMP-9 antibody reversed CEACAM6-induced invasion and migration. CEACAM6 overexpression/siRNA knockdown, phospho-AKT immunoblotting, MMP-9 activity assay, LY294002 PI3K inhibitor treatment, EMT marker immunoblotting, peritoneal metastasis in vivo model PloS one Medium 25398131
2014 CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling; overexpressed CEACAM6 increased phosphorylation of FAK and paxillin; FAK inhibitor Y15 reduced tubule and vasculogenic mimicry formation in vitro; CEACAM6 overexpression increased VEGF expression and vasculogenic mimicry structures in vivo. CEACAM6 overexpression/siRNA knockdown, tubule formation assay with HUVECs, 3D-culture vasculogenic mimicry assay, FAK/paxillin phosphorylation immunoblotting, FAK inhibitor Y15, VEGF measurement, in vivo xenograft Biochimica et biophysica acta Medium 25703140
2014 CEACAM6 promoter activity is regulated by HIF-1 binding to hypoxia-responsive elements (HREs); methylation of CpG sites within these HREs inversely correlates with CEACAM6 expression; dietary low-methyl conditions in transgenic human CEACAM6 mice led to HRE demethylation, increased CEACAM6 expression, and enhanced AIEC colonization. Bisulfite sequencing, SnapShot site-specific methylation analysis, pCpGfree reporter system, transgenic mice expressing human CEACAM6 fed low-methyl diet, bacterial colonization quantification, cytokine measurement Gut High 24898815
2017 CEACAM6 promotes OSCC invasion, migration, and metastasis through physical interaction with EGFR and enhancement of EGFR activation, clustering, and intracellular signaling cascades; this function requires N-glycosylation at Asn256 (N256) mediated by MGAT5 (α-1,6-mannosylglycoprotein 6-β-N-acetylglucosaminyltransferase); a CEACAM6-specific antibody blocked EGFR signaling and invasion. Co-immunoprecipitation of CEACAM6-EGFR interaction, MGAT5 knockdown, N256 site-directed mutagenesis, invasion/migration assays, cytoskeletal rearrangement assay, in vivo metastasis model, anti-CEACAM6 sdAb/HCAb treatment Oncogene High 28892050
2017 CEACAM6 on cancer cells acts as an immune checkpoint by binding to CEACAM1 expressed on activated tumor-specific T cells, suppressing T cell-mediated antitumor activity; blocking the CEACAM6-CEACAM1 interaction with humanized antibody BAY 1834942 restored T cell cytokine secretion and cancer cell killing. Co-culture experiments with T cells and cancer cells, CEACAM6-blocking antibody treatment, cytokine secretion measurement, T cell killing assay, comparison to anti-PD-1/PD-L1/TIM-3 antibodies Oncoimmunology Medium 35141051
2017 Candida albicans binds directly to the extracellular N-terminal IgV-like domain of CEACAM6 (and CEACAM1, -3, -5); CEACAM6 engagement leads to increased soluble CEACAM6 expression in enterocytes; soluble CEACAM6 reduces C. albicans-induced CXCL8 secretion; CEACAM1 is required for CXCL8 response. Direct binding assay of C. albicans to recombinant CEACAM ectodomains, shRNA CEACAM1 knockdown, CXCL8 ELISA, CEACAM1 phosphorylation immunoblotting, flow cytometry mBio Medium 28292985
2019 CRISPR/Cas9 knockout of CEACAM6 in HPAF-II pancreatic ductal adenocarcinoma cells alters ECM-cell adhesion, catabolism, immune environment, transmembrane transport, and autophagy as shown by quantitative proteomics; CEACAM6 loss increases mitochondrial basal and maximal respiratory capacity; CEACAM6-/- cells show >65% growth suppression in vivo. CRISPR/Cas9 knockout, quantitative proteomics (mass spectrometry), Seahorse mitochondrial bioenergetics assay, nude mouse xenograft Scientific reports High 31797958
2020 miR-146a and miR-26a post-transcriptionally regulate CEACAM6 expression in lung adenocarcinoma cells, verified by luciferase reporter assay; CEACAM6 promotes cisplatin resistance by affecting EMT and stemness markers (N-cadherin, vimentin, Sox2, Oct4, GTP-RhoA upregulation; E-cadherin downregulation); both miRNAs counteract these CEACAM6-mediated effects. Luciferase reporter assay for miRNA targeting, CEACAM6 knockdown/overexpression, IC50 determination, EMT and stemness marker immunoblotting, invasion/migration assays Thoracic cancer Medium 32648688
2021 CD151 forms physical complexes with CEACAM6, as confirmed by co-immunoprecipitation, pull-down assay, and immunofluorescence; CD151 silencing downregulates CEACAM6 expression both in vitro and in vivo, acting through TGFβ1 regulation, linking CD151 to CEACAM6 in colorectal cancer signaling. Co-immunoprecipitation, mass spectrometry, pull-down assay, immunofluorescence, RNA-seq, CD151 siRNA knockdown, xenograft International journal of biological sciences Medium 33767593
2022 CEACAM6 homophilic interactions on lung cancer cell surfaces activate the Src-FAK signaling pathway and inhibit anoikis; recombinant CEACAM6 treatment of cells induced homophilic interactions in the cell membrane and activated Src-FAK; CEACAM6 was predominantly present on the cancer cell surface rather than secreted. CellphoneDB analysis on scRNA-seq, CEACAM6 protein treatment of cells, immunoblotting for Src/FAK phosphorylation, anoikis assay, ELISA and immunoblotting of conditioned media and cell fractions Translational oncology Medium 35358791
2023 CEACAM6 protein stability is enhanced through lysine lactylation downstream of ALDOB-mediated lactagenesis; the ALDOB/PDK1/lactate/CEACAM6 axis promotes CRC cell proliferation and chemoresistance; secreted lactate activates PDK1 which mediates CEACAM6 expression effects; CEACAM6 knockdown reversed the ALDOB-mediated proliferation and chemoresistance phenotype. Cell-based assays, PDK1 activation analysis, lactate measurement, CEACAM6 knockdown, lysine lactylation detection, LDHB expression analysis Cell death & disease Medium 37816733
2008 A novel intron-retention isoform of rat CEACAM6 (Ceacam6-L) contains a transmembrane domain and intracellular region (rather than GPI anchor), is exclusively expressed in rat testis from 5 weeks postnatal, and localizes specifically to the interface between Sertoli cells and elongated spermatids at the apical ectoplasmic specialization (not the blood-testis barrier), suggesting a role in spermatid anchoring and spermiation. RT-PCR, Northern blot, immunoblot, immunohistochemistry, confocal laser scanning microscopy with anti-CEACAM6-L antibody Biology of reproduction Medium 18685128
2015 CEACAM6 promotes cell proliferation in pancreatic carcinoma by increasing cyclin D1 and CDK4 protein levels; siRNA knockdown of CEACAM6 decreased cyclin D1 and CDK4 levels while overexpression increased them. siRNA knockdown and forced CEACAM6 overexpression in multiple pancreatic cancer cell lines, immunoblotting for cyclin D1 and CDK4, proliferation assay, in vivo xenograft Oncology reports Medium 26497080
2023 CEACAM6 acts as a negative regulator of HO-1 (heme oxygenase-1)-mediated antioxidant defense in human alveolar type 2 epithelial cells; CEACAM6 overexpression increased nitrosative/oxidative stress and cell death upon CSE treatment; this was confirmed in human precision-cut lung slices using AAV-mediated gene transduction. CSE-resistant cell line model, transcriptomic profiling, AAV-mediated CEACAM6 overexpression in precision-cut lung slices, 3-nitrotyrosine measurement, HO-1 activity inhibition American journal of respiratory and critical care medicine Medium 37219322
2020 CEACAM6 on follicle-associated epithelium (FAE) mediates translocation of AIEC LF82 across the intestinal epithelium in Crohn's disease; bacterial LF82 passage required both bacterial long polar fimbriae (LPF) and host CEACAM6; anti-CEACAM6 antibody inhibited bacterial translocation and prevented LF82-induced increases in paracellular permeability. In vitro FAE model, Ussing chamber experiments with patient CD FAE tissue, LPF-deletion mutant bacteria, anti-CEACAM6 antibody blocking, 51Chromium-EDTA paracellular permeability assay, immunofluorescence/immunoblot for CEACAM6 expression Journal of Crohn's & colitis High 31393983

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. The Journal of clinical investigation 450 17525800
1989 Cell adhesion activity of non-specific cross-reacting antigen (NCA) and carcinoembryonic antigen (CEA) expressed on CHO cell surface: homophilic and heterophilic adhesion. Biochemical and biophysical research communications 260 2803308
2007 Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC cancer 207 17201906
2005 Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen). Cancer research 176 16204051
2004 CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells. Oncogene 161 14724575
2000 Carcinoembryonic antigen family members CEACAM6 and CEACAM7 are differentially expressed in normal tissues and oppositely deregulated in hyperplastic colorectal polyps and early adenomas. The American journal of pathology 158 10666389
1988 Characterization of a cDNA clone for the nonspecific cross-reacting antigen (NCA) and a comparison of NCA and carcinoembryonic antigen. The Journal of biological chemistry 143 2830274
1996 CD66a, CD66b, CD66c, and CD66d each independently stimulate neutrophils. Journal of leukocyte biology 120 8699114
1991 A specific heterotypic cell adhesion activity between members of carcinoembryonic antigen family, W272 and NCA, is mediated by N-domains. The Journal of biological chemistry 115 2022629
2008 A putative cation channel, NCA-1, and a novel protein, UNC-80, transmit neuronal activity in C. elegans. PLoS biology 99 18336069
2005 CEACAM6 is a novel biomarker in pancreatic adenocarcinoma and PanIN lesions. Annals of surgery 78 15729073
1992 Subcellular localization of CD66, CD67, and NCA in human neutrophils. Journal of leukocyte biology 77 1640165
2007 UNC-80 and the NCA ion channels contribute to endocytosis defects in synaptojanin mutants. Current biology : CB 74 17825559
1990 Expression of the CD15 differentiation antigen (3-fucosyl-N-acetyl-lactosamine, LeX) on putative neutrophil adhesion molecules CR3 and NCA-160. The Biochemical journal 74 1694660
1993 Expression of carcinoembryonic antigen (CEA) and nonspecific crossreacting antigen (NCA) in gastrointestinal cancer; the correlation with degree of differentiation. British journal of cancer 73 8318403
1985 Two CEA and three NCA species, although distinguishable by monoclonal antibodies, have nearly identical peptide patterns. International journal of cancer 71 3839768
2014 CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway. PloS one 63 25398131
2004 CEACAM6 is a determinant of pancreatic adenocarcinoma cellular invasiveness. British journal of cancer 63 15316565
2008 Overexpression of CEACAM6 promotes migration and invasion of oestrogen-deprived breast cancer cells. European journal of cancer (Oxford, England : 1990) 62 18614350
2021 Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. Nature communications 61 33674603
2015 Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies. Clinical cancer drugs 57 27595061
1993 Neutrophil NCA-160 (CD66) is the major protein carrier of selectin binding carbohydrate groups LewisX and sialyl lewisX. Biochemical and biophysical research communications 57 7689841
1991 The high lysability by LAK cells of colon-carcinoma cells resistant to doxorubicin is associated with a high expression of ICAM-1, LFA-3, NCA and a less-differentiated phenotype. International journal of cancer 57 1706327
2015 The NCA sodium leak channel is required for persistent motor circuit activity that sustains locomotion. Nature communications 54 25716181
2023 Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect. Cell death & disease 53 37816733
2015 CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling. Biochimica et biophysica acta 53 25703140
2012 CD66c is a novel marker for colorectal cancer stem cell isolation, and its silencing halts tumor growth in vivo. Cancer 52 23027178
2007 GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin alpha5beta1-fibronectin interaction. Journal of cellular physiology 51 17167768
2020 α-Amino acid N-carboxyanhydride (NCA)-derived synthetic polypeptides for nucleic acids delivery. Advanced drug delivery reviews 50 33333206
2013 CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and metastasis in pancreatic cancer. International journal of oncology 50 23857344
2007 CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling. Oncogene 49 17653079
2024 The emerging roles of CEACAM6 in human cancer (Review). International journal of oncology 48 38240103
2019 Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target. Scientific reports 48 31797958
2018 Advances and Biomedical Applications of Polypeptide Hydrogels Derived from α-Amino Acid N-Carboxyanhydride (NCA) Polymerizations. Advanced healthcare materials 48 29869375
2004 CEACAM6 cross-linking induces caveolin-1-dependent, Src-mediated focal adhesion kinase phosphorylation in BxPC3 pancreatic adenocarcinoma cells. The Journal of biological chemistry 47 15047698
2001 Identification and comparison of residues critical for cell-adhesion activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8. Journal of leukocyte biology 47 11590190
1983 Immunohistochemical localization of carcinoembryonic antigen (CEA), CEA-S, and nonspecific cross-reacting antigen (NCA) in carcinomas of lung. Cancer 42 6311398
2017 Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation. Oncogene 41 28892050
2004 c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components. Biochemical and biophysical research communications 41 15047158
1988 Carcinoembryonic antigen family: characterization of cDNAs coding for NCA and CEA and suggestion of nonrandom sequence variation in their conserved loop-domains. Genomics 40 3220478
2022 Overexpression of CEACAM6 activates Src-FAK signaling and inhibits anoikis, through homophilic interactions in lung adenocarcinomas. Translational oncology 39 35358791
2010 Synthesis and characterization of poly-L-lysine-grafted silica nanoparticles synthesized via NCA polymerization and click chemistry. Langmuir : the ACS journal of surfaces and colloids 38 20337478
1998 Expression of four CEA family antigens (CEA, NCA, BGP and CGM2) in normal and cancerous gastric epithelial cells: up-regulation of BGP and CGM2 in carcinomas. International journal of cancer 38 9533775
2014 Diet-induced hypoxia responsive element demethylation increases CEACAM6 expression, favouring Crohn's disease-associated Escherichia coli colonisation. Gut 37 24898815
2011 Role of four calcium transport proteins, encoded by nca-1, nca-2, nca-3, and cax, in maintaining intracellular calcium levels in Neurospora crassa. Eukaryotic cell 37 21335528
2009 Design and activity of a murine and humanized anti-CEACAM6 single-chain variable fragment in the treatment of pancreatic cancer. Cancer research 37 19244123
1999 Four carcinoembryonic antigen subfamily members, CEA, NCA, BGP and CGM2, selectively expressed in the normal human colonic epithelium, are integral components of the fuzzy coat. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 10436421
1989 Expression of an NCA cDNA in NIH/3T3 cells yields a 110K glycoprotein, which is anchored into the membrane via glycosyl-phosphatidylinositol. Biochemical and biophysical research communications 37 2742579
2021 T cell-mediated elimination of cancer cells by blocking CEACAM6-CEACAM1 interaction. Oncoimmunology 36 35141051
2004 Overexpression of CEACAM6 promotes insulin-like growth factor I-induced pancreatic adenocarcinoma cellular invasiveness. Oncogene 36 15208677
2000 Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: differences in dosimetry and biokinetics of 188Re- and 99mTc-labeled anti-NCA-95 MAbs. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 34 10716329
2017 Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells. mBio 33 28292985
2005 Myeloid antigens in childhood lymphoblastic leukemia: clinical data point to regulation of CD66c distinct from other myeloid antigens. BMC cancer 33 15826304
1992 Three different NCA species, CGM6/CD67, NCA-95, and NCA-90, are comprised in the major 90 to 100-kDa band of granulocyte NCA detectable upon SDS-polyacrylamide gel electrophoresis. Biochemical and biophysical research communications 33 1370882
2010 Abnormal CEACAM6 expression in Crohn disease patients favors gut colonization and inflammation by adherent-invasive E. coli. Virulence 32 21178454
1988 Protein analysis of NCA-50 shows identity to NCA cDNA deduced sequences and indicates posttranslational modifications. Biochemical and biophysical research communications 32 3390172
2017 A CEACAM6-High Airway Neutrophil Phenotype and CEACAM6-High Epithelial Cells Are Features of Severe Asthma. Journal of immunology (Baltimore, Md. : 1950) 31 28275137
2015 Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity. Biomaterials 31 26204223
2012 Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells. European journal of cancer (Oxford, England : 1990) 30 22918079
2012 Influenza A virus neuraminidase protein enhances cell survival through interaction with carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) protein. The Journal of biological chemistry 29 22396546
1983 Minor serine tRNA containing anticodon NCA (C4 RNA) from human and mouse cells. Biochemistry international 29 6435631
2004 CEACAM6 as a novel target for indirect type 1 immunotoxin-based therapy in pancreatic adenocarcinoma. Biochemical and biophysical research communications 28 15081416
2014 CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer. Acta biochimica et biophysica Sinica 27 24492534
2012 Focal overexpression of CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis. Molecular cancer 27 23021083
2009 CEACAM6 attenuates adenovirus infection by antagonizing viral trafficking in cancer cells. The Journal of clinical investigation 27 19411761
2024 Delivery of a BET protein degrader via a CEACAM6-targeted antibody-drug conjugate inhibits tumour growth in pancreatic cancer models. Nature communications 26 38467634
2020 Colorectal cancer screening: Assessment of CEACAM6, LGALS4, TSPAN8 and COL1A2 as blood markers in faecal immunochemical test negative subjects. Journal of advanced research 26 32257432
2007 High expression of CEACAM6 and CEACAM8 mRNA in acute lymphoblastic leukemias. Annals of hematology 25 17909799
2020 Enhanced E. coli LF82 Translocation through the Follicle-associated Epithelium in Crohn's Disease is Dependent on Long Polar Fimbriae and CEACAM6 expression, and Increases Paracellular Permeability. Journal of Crohn's & colitis 24 31393983
2018 Development and evaluation of a CEACAM6-targeting theranostic nanomedicine for photoacoustic-based diagnosis and chemotherapy of metastatic cancer. Theranostics 24 30128051
2012 Molecular targeting of CEACAM6 using antibody probes of different sizes. Journal of controlled release : official journal of the Controlled Release Society 24 22568933
2011 A co-operative regulation of neuronal excitability by UNC-7 innexin and NCA/NALCN leak channel. Molecular brain 24 21489288
2021 Comprehensive RNA analysis of CSF reveals a role for CEACAM6 in lung cancer leptomeningeal metastases. NPJ precision oncology 23 34625644
2013 Significance of CD66c expression in childhood acute lymphoblastic leukemia. Leukemia research 23 24231528
1994 Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell origin. Leukemia 23 7808000
2019 Therapeutic Effect of pHLIP-mediated CEACAM6 Gene Silencing in Lung Adenocarcinoma. Scientific reports 22 31474761
2016 CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer. Oncotarget 22 27421133
1998 CD66c antigen expression is myeloid restricted in normal bone marrow but is a common feature of CD10+ early-B-cell malignancies. Tissue antigens 22 9714468
2020 CEACAM6 promotes cisplatin resistance in lung adenocarcinoma and is regulated by microRNA-146a and microRNA-26a. Thoracic cancer 21 32648688
2017 The NCA-1 and NCA-2 Ion Channels Function Downstream of Gq and Rho To Regulate Locomotion in Caenorhabditis elegans. Genetics 21 28325749
2017 Dopamine negatively modulates the NCA ion channels in C. elegans. PLoS genetics 21 28968387
2015 Diagnostic performance of CD66c in lung adenocarcinoma-associated malignant pleural effusion: comparison with CEA, CA 19-9, and CYFRA 21-1. Pathology 21 25551300
1996 Analysis of heterophilic cell adhesion mediated by CD66b and CD66c using their soluble recombinant proteins. Biochemical and biophysical research communications 21 8645267
2023 CEACAM6 as a Novel Therapeutic Target to Boost HO-1-mediated Antioxidant Defense in COPD. American journal of respiratory and critical care medicine 20 37219322
2008 Expression of CD66c and CD25 in acute lymphoblastic leukemia as a predictor of the presence of BCR/ABL rearrangement. Hematology/oncology and stem cell therapy 20 20063526
1999 The KOR-SA3544 antigen predominantly expressed on the surface of Philadelphia chromosome-positive acute lymphoblastic leukemia cells is nonspecific cross-reacting antigen-50/90 (CD66c) and invariably expressed in cytoplasm of human leukemia cells. Leukemia 20 10374883
2014 A marker of endocrine receptor-positive cells, CEACAM6, is shared by two major classes of breast cancer: luminal and HER2-enriched. The American journal of pathology 19 24655379
2011 CD66c expression in B-cell acute lymphoblastic leukemia: strength and weakness. International journal of laboratory hematology 18 20666852
2010 Synthesis and characterization of Fe3O4@SiO2@poly-L-alanine, peptide brush-magnetic microspheres through NCA chemistry for drug delivery and enrichment of BSA. Colloids and surfaces. B, Biointerfaces 18 20728321
2008 Intron retention generates a novel isoform of CEACAM6 that may act as an adhesion molecule in the ectoplasmic specialization structures between spermatids and sertoli cells in rat testis. Biology of reproduction 18 18685128
2022 CEACAM6 serves as a biomarker for leptomeningeal metastasis in lung adenocarcinoma. Cancer medicine 17 36082960
2021 CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFβ1. International journal of biological sciences 17 33767593
2016 The Role of Biliary Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 6 (CEACAM6) as a Biomarker in Cholangiocarcinoma. PloS one 17 26974538
1993 Nonspecific crossreacting antigen (NCA) is a major member of the carcinoembryonic antigen (CEA)-related gene family expressed in lung cancer. British journal of cancer 17 7678982
2024 CEACAM6 expression and function in tumor biology: a comprehensive review. Discover oncology 15 38796667
2022 In high-grade ovarian carcinoma, platinum-sensitive tumor recurrence and acquired-resistance derive from quiescent residual cancer cells that overexpress CRYAB, CEACAM6, and SOX2. The Journal of pathology 15 35302657
2015 Cell motility and spreading promoted by CEACAM6 through cyclin D1/CDK4 in human pancreatic carcinoma. Oncology reports 15 26497080
2008 Overexpression of CEACAM6 in borderline and invasive mucinous ovarian neoplasms. Gynecologic oncology 15 18331757
2015 BCR-ABL1 and CD66c exhibit high concordance in minimal residual disease detection of adult B-acute lymphoblastic leukemia. American journal of translational research 14 26045902
2008 Differential expression of the carcinoembryonic antigen-related cell adhesion molecules panCD66, CD66a, CD66c and of sialyl-Lewis x (CD15s) on blast cells of acute leukemias. International journal of hematology 14 18299959

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