Affinage

CEACAM6

Cell adhesion molecule CEACAM6 · UniProt P40199

Length
344 aa
Mass
37.2 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEACAM6 is a GPI-anchored immunoglobulin superfamily glycoprotein that functions as a versatile cell-surface adhesion molecule and signaling scaffold, mediating homo- and heterophilic adhesion through its N-terminal IgV-like domain, serving as a receptor for diverse pathogens, and modulating intracellular survival and invasion pathways in both immune and epithelial cells (PMID:2830274, PMID:2742579, PMID:2022629, PMID:11590190). In cancer cells, CEACAM6 activates a caveolin-1/c-Src/FAK/AKT signaling axis that confers anoikis resistance, promotes epithelial-mesenchymal transition via PI3K/AKT, enhances invasion through MMP-9 upregulation, and co-clusters with integrins (α5β1, αvβ3) to augment extracellular matrix adhesion (PMID:15047698, PMID:14724575, PMID:15316565, PMID:17167768, PMID:25398131). On mucosal epithelia, CEACAM6 serves as a receptor for adherent-invasive E. coli type 1 pili and Candida albicans, with its expression regulated by HIF-1 promoter elements whose methylation status controls inducibility, and by TGF-β/Smad3 signaling (PMID:17525800, PMID:28292985, PMID:24898815, PMID:17653079). CEACAM6 on tumor cells also functions as an immune checkpoint by engaging CEACAM1 on T cells to suppress anti-tumor cytotoxicity (PMID:35141051).

Mechanistic history

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

    Establishing the molecular identity of CEACAM6 as a CEA family member with a truncated domain structure resolved the relationship between NCA and CEA and predicted GPI-anchoring based on C-terminal hydrophobicity.

    Evidence cDNA cloning and sequencing from SW403 colon carcinoma library

    PMID:2830274

    Open questions at the time
    • GPI-anchor was predicted from sequence but not yet biochemically demonstrated
    • no functional role assigned
  2. 1989 High

    Demonstrating that CEACAM6 is tethered to the cell membrane via a GPI linkage established that it lacks an intracellular signaling domain, implying that downstream signaling must occur through lateral membrane interactions.

    Evidence PI-PLC release of NCA from transfected NIH/3T3 cells detected by flow cytometry and immunoprecipitation

    PMID:2742579

    Open questions at the time
    • identity of signaling co-receptors unknown
    • no adhesion function yet tested
  3. 1991 High

    Mapping the adhesion specificity of CEACAM6 to its N-terminal domain established that this single domain mediates both homophilic and heterophilic (with CEACAM8) cell adhesion, defining CEACAM6 as an adhesion molecule.

    Evidence CHO transfectants with chimeric N-domain constructs in cell aggregation assays

    PMID:11590190 PMID:2022629 PMID:8645267

    Open questions at the time
    • structural basis of N-domain binding interface unresolved
    • in vivo adhesion relevance not demonstrated
  4. 1992 High

    Localizing CEACAM6 to neutrophil secondary granules and identifying it as the major carrier of sialyl-LewisX selectin ligands revealed a role in neutrophil activation and leukocyte-endothelial interactions.

    Evidence Subcellular fractionation of neutrophils; immunoprecipitation with anti-CD15 antibody; neutrophil-HUVEC adhesion assays with calcium chelation

    PMID:1640165 PMID:1694660 PMID:7689841 PMID:8699114

    Open questions at the time
    • precise mechanism of CEACAM6 signaling from GPI anchor on neutrophils unclear
    • selectin binding is indirect (via carbohydrate); direct protein-protein selectin interaction not shown
  5. 2004 High

    A burst of studies in pancreatic cancer revealed that CEACAM6 signals through caveolin-1-dependent c-Src to phosphorylate FAK and activate AKT, conferring anoikis resistance, enhancing ECM adhesion via integrin αvβ3 cross-talk, and promoting invasion through MMP-9 — establishing CEACAM6 as a pro-metastatic signaling hub.

    Evidence Antibody cross-linking, siRNA knockdown, dominant-negative Src, orthotopic xenograft models, caspase profiling, zymography in BxPC3 and Capan2 pancreatic cancer cells

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

    Open questions at the time
    • how a GPI-anchored protein activates caveolin-1/Src mechanistically is not resolved at the structural level
    • relative contribution of each integrin (αvβ3 vs α5β1) not dissected in same system
  6. 2007 High

    Identifying CEACAM6 as the receptor for AIEC type-1 pili on ileal epithelium, and showing that co-clustering with integrin α5β1 enhances fibronectin matrix assembly, extended CEACAM6's roles to mucosal pathogen recognition and epithelial differentiation control.

    Evidence Primary ileal enterocyte adhesion assays with anti-CEACAM6 blocking; confocal co-clustering with integrin α5β1; fibronectin binding and anoikis assays

    PMID:17167768 PMID:17525800

    Open questions at the time
    • structural basis of type-1 pilus-CEACAM6 interaction not resolved
    • whether integrin co-clustering is direct or lipid-raft mediated is unknown
  7. 2007 High

    Demonstrating that TGF-β/Smad3 transcriptionally activates the CEACAM6 promoter placed CEACAM6 expression under the control of a major growth-factor pathway relevant to both normal differentiation and cancer.

    Evidence Promoter reporter assays, rescue in TGF-β receptor-mutant and Smad3-deficient cell lines, Smad3 knockout mouse gastric tissue

    PMID:17653079

    Open questions at the time
    • whether Smad3 binds the promoter directly or through a co-factor complex is unclear
    • relationship between Smad3 and HIF-1 regulation of the same promoter not integrated
  8. 2012 High

    Showing that influenza neuraminidase physically interacts with CEACAM6 to activate Src/FAK/AKT and promote host-cell survival expanded CEACAM6's pathogen-receptor role beyond bacteria to viruses and revealed pathogen exploitation of the same pro-survival signaling axis used in cancer.

    Evidence Co-immunoprecipitation of NA with CEACAM6, siRNA knockdown in lung cells, phospho-immunoblotting, viral titer measurement

    PMID:22396546

    Open questions at the time
    • binding interface on CEACAM6 for neuraminidase not mapped
    • relevance to in vivo influenza pathogenesis not tested
  9. 2014 High

    Revealing that HIF-1-responsive element methylation in the CEACAM6 promoter gates its expression, and that dietary methyl depletion causes aberrant CEACAM6 expression enabling AIEC colonization, linked epigenetic regulation to intestinal pathogenesis.

    Evidence Bisulfite sequencing, CpG-free reporter assay, transgenic CEACAM6 mice on low-methyl diet with AIEC quantification

    PMID:24898815

    Open questions at the time
    • which DNA methyltransferases maintain HRE methylation not identified
    • whether HIF-1 and Smad3 co-regulate the promoter in the same cells is unexplored
  10. 2017 High

    Demonstrating that N-glycosylation at Asn256 (mediated by MGAT5) is required for CEACAM6-EGFR interaction and downstream signaling in oral cancer, and that C. albicans binds the N-domain of CEACAM6 to modulate epithelial immune responses, revealed glycan-dependent and -independent receptor functions.

    Evidence N256 mutagenesis, MGAT5 manipulation, CEACAM6-EGFR co-clustering; recombinant CEACAM6 domain binding to C. albicans, CXCL8 ELISA

    PMID:28292985 PMID:28892050

    Open questions at the time
    • structural model of glycan-dependent CEACAM6-EGFR complex lacking
    • full repertoire of fungal adhesins for CEACAM6 not identified
  11. 2021 High

    Establishing that CEACAM6 on tumor cells engages CEACAM1 on T cells to suppress anti-tumor immunity identified CEACAM6 as an immune checkpoint ligand, paralleling PD-L1 biology.

    Evidence T cell-cancer cell co-cultures with CEACAM6-blocking antibody BAY 1834942, cytokine secretion and killing assays

    PMID:35141051

    Open questions at the time
    • whether CEACAM6-CEACAM1 checkpoint operates in vivo in patient tumors not validated
    • signaling events downstream of CEACAM1 engagement by CEACAM6 on T cells not dissected
  12. 2023 Medium

    Identifying lysine lactylation as a post-translational modification that stabilizes CEACAM6 protein downstream of ALDOB-mediated lactagenesis linked metabolic reprogramming (Warburg effect) to CEACAM6 protein abundance and chemoresistance.

    Evidence ALDOB and CEACAM6 gene silencing, lactylation inhibition, PDK1 activation studies, chemoresistance assays in CRC cells

    PMID:37816733

    Open questions at the time
    • specific lactylated lysine residues on CEACAM6 not mapped
    • whether lactylation affects CEACAM6 signaling activity or only stability is unknown
    • single-lab finding awaits independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CEACAM6 homophilic and heterophilic interactions at atomic resolution, how a GPI-anchored protein mechanistically activates Src-family kinases through caveolin-1, and whether CEACAM6-CEACAM1 immune checkpoint blockade provides therapeutic benefit in patients.
  • no crystal or cryo-EM structure of CEACAM6 N-domain in complex with any binding partner
  • mechanism linking GPI-anchor to caveolin-1-Src activation remains conceptual
  • clinical efficacy of anti-CEACAM6 checkpoint antibodies unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1500931 Cell-Cell communication 5 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
CAV1CD151CEACAM1CEACAM8EGFRITGA5ITGAV

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CEACAM6 acts as a receptor for adherent-invasive E. coli (AIEC) adhesion on the apical surface of ileal epithelial cells; AIEC adhesion is dependent on type 1 pili on the bacterial surface binding to CEACAM6, and IFN-γ or TNF-α stimulation increases CEACAM6 expression, promoting AIEC colonization. Primary ileal enterocyte adhesion assays, anti-CEACAM6 blocking, cytokine stimulation of cultured intestinal epithelial cells The Journal of clinical investigation High 17525800
1988 CEACAM6 (NCA) is encoded by a cDNA containing a 34-aa leader sequence, 310-aa mature protein with one immunoglobulin-like domain doublet (versus three in CEA), and a C-terminal hydrophobic domain; overall ~85% amino acid homology to CEA, supporting GPI-anchor membrane attachment. cDNA cloning and sequencing from SW403 colon carcinoma library; sequence comparison The Journal of biological chemistry High 2830274
1989 CEACAM6 (NCA) is anchored to the cell membrane via a glycosyl-phosphatidylinositol (GPI) linkage, demonstrated by release of surface NCA from transfected NIH/3T3 cells upon treatment with phosphatidylinositol-specific phospholipase C. Transfection of NCA cDNA into NIH/3T3 cells, PI-PLC treatment, flow cytometry and immunoprecipitation of surface glycoproteins Biochemical and biophysical research communications High 2742579
1991 CEACAM6 (NCA) mediates specific Ca2+-independent heterotypic cell adhesion with W272 (CGM6/CEACAM8), and this adhesion is mediated by the N-terminal domain of NCA; W272-expressing cells showed no homotypic binding but bound cells expressing NCA via NCA's N-domain. CHO cell transfectants expressing NCA, CEA, W272 and chimeric N-domain constructs; cell aggregation assays; chimeric domain analysis in COS-1 cells The Journal of biological chemistry High 2022629
1992 CEACAM6 (NCA species ~95-100 kDa) is localized predominantly in secondary granules of neutrophils, with lesser amounts in plasma membrane and primary granules, suggesting secondary granules as the intracellular reservoir from which CEACAM6 is recruited to the cell surface upon neutrophil activation. Nitrogen cavitation, differential centrifugation, SDS-PAGE and immunoblotting of neutrophil subcellular fractions Journal of leukocyte biology High 1640165
1996 CEACAM6 (CD66c) antibody binding to neutrophils triggers a calcium-dependent signal that upregulates CD11/CD18 on the neutrophil surface and increases adhesion to HUVEC monolayers; CD66c signals independently from other CD66 family members. Neutrophil adhesion assays to HUVEC monolayers, CD18 blocking antibody, calcium chelation, sequential desensitization experiments Journal of leukocyte biology High 8699114
2001 The N-terminal domain (N-domain) of CEACAM6 mediates both homophilic (CEACAM6–CEACAM6) and heterophilic (CEACAM6–CEACAM8) cell adhesion; homologue-scanning mutagenesis revealed overlapping but non-identical critical residues for each interaction, similar to sites used by Neisseria Opa proteins. CHO transfectants expressing mutant and chimeric CEACAM6/CEACAM8 proteins; cell aggregation assays; homologue-scanning mutagenesis Journal of leukocyte biology High 11590190
2004 CEACAM6 cross-linking in pancreatic adenocarcinoma cells activates c-Src, induces caveolin-1-dependent tyrosine phosphorylation of FAK (p125FAK), and increases cellular resistance to anoikis; FAK phosphorylation requires c-Src kinase activity. Antibody-mediated cross-linking of CEACAM6 in BxPC3 cells, immunoblotting for phospho-FAK and phospho-Src, caveolin-1 dependence assessed, anoikis resistance quantified The Journal of biological chemistry High 15047698
2004 CEACAM6 cross-linking initiates c-Src-dependent cross-talk with αvβ3 integrin, leading to increased pancreatic adenocarcinoma cell adhesion to fibronectin and vitronectin ECM components; this effect is blocked by Src inhibitor PP2 or c-Src-specific siRNA. Antibody-mediated CEACAM6 cross-linking, ECM adhesion assays, Src kinase inhibitor PP2, c-Src siRNA knockdown Biochemical and biophysical research communications High 15047158
2004 CEACAM6 gene silencing by siRNA increases susceptibility to caspase-mediated anoikis in pancreatic adenocarcinoma cells under anchorage-independent conditions, decreases Akt phosphorylation at Ser-473, and inhibits in vivo metastatic ability in orthotopic mouse xenograft models. siRNA knockdown, YO-PRO-1/PI flow cytometry for anoikis, caspase fluorometric profiling, Z-VAD-fmk rescue, Akt immunoblotting, orthotopic nude mouse xenograft Oncogene High 14724575
2004 CEACAM6 overexpression in pancreatic adenocarcinoma increases invasiveness in a c-Src-dependent manner; c-Src mediates CEACAM6-dependent matrix metalloproteinase-9 (MMP-9) activation that contributes to enhanced invasion. Stable retroviral overexpression and RNAi knockdown, modified Boyden chamber invasion assay, constitutively active/dominant-negative c-Src constructs, MMP-9 activity assay British journal of cancer High 15316565
2004 CEACAM6 overexpression enhances IGF-I-induced invasiveness through upregulation of IGF-IR expression and increased Akt and c-Src kinase activities, as well as elevated MMP-2 expression; Akt is both necessary and sufficient for IGF-IR upregulation, while c-Src is necessary but not sufficient. Stable CEACAM6 overexpression in Capan2 cells, invasion assays toward IGF-I, anti-IGF-IR blocking antibody, Akt and c-Src inhibitors, MMP-2 zymography Oncogene High 15208677
2007 CEACAM6 (and CEA) co-clusters with integrin α5β1 on the cell surface and enhances binding of integrin α5β1 to fibronectin without changing surface integrin levels, leading to increased fibronectin matrix assembly (polymerized fibronectin 'cocoon') and inhibition of cellular differentiation and anoikis; disruption of fibronectin binding or integrin α5β1 restores differentiation and anoikis. Confocal microscopy co-clustering analysis, fibronectin binding assays, antibody blocking of fibronectin and integrin α5β1, anoikis assays Journal of cellular physiology High 17167768
2007 CEACAM5 and CEACAM6 promoters are activated by TGF-β signaling through Smad3; restoration of TGF-β signaling (via TGF-β type II receptor or Smad3) in non-responsive gastric cancer cell lines induced CEACAM5 and CEACAM6 expression, and CEA expression was markedly decreased in Smad3 null mice. Reporter assays for CEACAM5/CEACAM6 promoters, rescue of TGF-β signaling in receptor-mutant and Smad3-deficient cell lines, Smad3 knockout mouse gastric tissue analysis Oncogene High 17653079
2009 CEACAM6 antagonizes the Src signaling pathway in pancreatic cancer cells, downregulates cytoskeleton proteins, and blocks adenovirus trafficking to the nucleus; siRNA knockdown of CEACAM6 enhances adenoviral replication and antitumor effect of oncolytic adenovirus in vivo. CEACAM6 overexpression and siRNA knockdown, Src signaling immunoblotting, cytoskeleton protein analysis, adenovirus nuclear trafficking assays, mouse xenograft model The Journal of clinical investigation High 19411761
2012 Influenza A virus neuraminidase (NA) protein interacts with CEACAM6 (C6) and activates the Src/Akt signaling axis (increased phosphorylation of Src, FAK, Akt, GSK3β, Bcl-2), enhancing host cell survival; siRNA knockdown of CEACAM6 reduces Src/FAK/Akt activation, increases apoptosis, and reduces viral titers. Co-immunoprecipitation of NA with CEACAM6, siRNA knockdown in human lung adenocarcinoma and normal bronchial epithelial cells, phospho-immunoblotting, apoptosis assays, viral titer measurement The Journal of biological chemistry High 22396546
2013 CEACAM6 promotes EMT and pancreatic cancer invasion and metastasis; miR-29a/b/c directly targets CEACAM6 and suppresses its expression at the post-transcriptional level, reducing EMT, migration, and invasion. CEACAM6 overexpression and shRNA knockdown, in vitro invasion/migration assays, in vivo metastasis models, miRNA transfection with EMT marker immunoblotting International journal of oncology Medium 23857344
2014 CEACAM6 promotes EMT and invasion in gastric cancer via PI3K/AKT signaling; CEACAM6 overexpression increases N-cadherin, vimentin, Slug and MMP-9 while decreasing E-cadherin; PI3K inhibitor LY294002 reverses CEACAM6-induced EMT; anti-MMP-9 antibody reverses CEACAM6-induced invasion. CEACAM6 overexpression/silencing in GC cells, EMT marker immunoblotting, MMP-9 antibody blocking, PI3K inhibitor treatment, peritoneal metastasis in vivo model PloS one Medium 25398131
2015 CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling; CEACAM6 overexpression increases phosphorylation of FAK and paxillin, and FAK inhibitor Y15 reduces tubule and vasculogenic mimicry formation. CEACAM6 overexpression/silencing, HUVEC tubule formation assay, 3D-culture vasculogenic mimicry assay, FAK inhibitor Y15 treatment, paxillin and FAK phospho-immunoblotting, xenograft in vivo Biochimica et biophysica acta Medium 25703140
2017 CEACAM6 promotes OSCC invasion, migration, cytoskeletal rearrangement, and metastasis by interacting with EGFR and enhancing EGFR activation, clustering, and intracellular signaling; N-glycosylation of CEACAM6 at Asn256, mediated by MGAT5, is critical for this EGFR interaction and signaling. Anti-CEACAM6 antibody (TMU HCAb) that specifically recognizes glycosylated CEACAM6, MGAT5 manipulation, CEACAM6 N256 mutagenesis, invasion/migration assays, EGFR co-clustering analysis, in vivo metastasis model Oncogene High 28892050
2008 CEACAM6 suppression by siRNA reverses migration and invasion of oestrogen-deprived resistant breast cancer cells and significantly reduces phosphorylated Akt and c-Src expression, placing CEACAM6 upstream of Akt and c-Src in mediating invasion. siRNA knockdown, migration and invasion assays, phospho-Akt and phospho-c-Src immunoblotting European journal of cancer Medium 18614350
2010 CEACAM6 cross-linking in B-cell precursor ALL cells activates Erk1/2, Akt, and p38 MAPK phosphorylation and upregulates integrin expression and integrin ligand (VCAM-1, ICAM-1) binding, but paradoxically increases apoptosis, unlike other GPI-anchored molecules such as CD24. Anti-CEACAM6 antibody cross-linking, flow cytometry for integrin expression and ligand binding, phospho-immunoblotting for Erk1/2/Akt/p38, apoptosis assays Experimental hematology Medium 20380867
2012 CEACAM6 overexpression in HNSCC enhances tumor growth and tumor-initiating activity by activating AKT and suppressing caspase-3-mediated cell death; PI3K/AKT inhibitors selectively ablate CEACAM6-expressing HNSCC foci in xenograft models. shRNA knockdown and viral overexpression of CEACAM6, xenograft mouse model, AKT inhibitor treatment, caspase-3 immunoblotting Molecular cancer Medium 23021083
1990 CEACAM6 (NCA-160, CD66c) is the predominant neutrophil surface carrier of CD15 (LewisX) and sialyl-LewisX carbohydrate antigens; NCA-90 and related NCAs do not express CD15. Immunoprecipitation and immunoblotting with anti-CD15 monoclonal antibody MC2; surface expression studies after fMLP stimulation The Biochemical journal Medium 1694660
1993 CEACAM6 (NCA-160, CD66c) is the major protein carrier of LewisX and sialyl LewisX groups on neutrophils that interact with vascular selectins E- and P-selectin; differently glycosylated forms of NCA are independently regulated on the cell surface. Immunoprecipitation and surface expression analysis after fMLP stimulation; flow cytometry for NCA species and sialyl/non-sialyl LewisX Biochemical and biophysical research communications Medium 7689841
1996 CD66b and CD66c (CEACAM6) mediate heterophilic cell adhesion through N-domain interactions; deglycosylated recombinant proteins retain adhesion activity (carbohydrate not required); CD66b/CD66c adhesion induces superoxide anion release from activated neutrophils. Soluble recombinant proteins from silkworm larvae, CHO transfectant adhesion assays, deglycosylation experiment, superoxide anion release assay Biochemical and biophysical research communications High 8645267
2008 A novel CEACAM6 isoform (CEACAM6-L) generated by intron retention encodes a protein with a transmembrane domain and intracellular region (unlike GPI-anchored CEACAM6), is exclusively expressed in rat testis starting at 5 weeks postnatal, and localizes to the interface between Sertoli cells and spermatids at apical ectoplasmic specializations, suggesting a role in spermatid anchoring. Differential display, RT-PCR, Northern blot, immunoblotting, confocal laser scanning microscopy/immunohistochemistry in rat testis Biology of reproduction Medium 18685128
2014 HIF-1-responsive element (HRE) methylation in the CEACAM6 promoter inversely correlates with CEACAM6 expression; low-methyl diet causes HRE demethylation in transgenic CEACAM6-expressing mice, leading to abnormal gut CEACAM6 expression and enhanced AIEC colonization and inflammation. Bisulfite sequencing, site-specific methylation SnapShot, pCpGfree promoter reporter assay, Smad3 knockout mice, transgenic CEACAM6 mice on low-methyl diet, AIEC quantification Gut High 24898815
2017 C. albicans binds directly to the extracellular N-terminal IgV-like domain of CEACAM6 (and CEACAM1, -3, -5); fungal binding to CEACAM1 and CEACAM6 in intestinal epithelial cells induces CEACAM1 tyrosine phosphorylation and alters epithelial immune responses (CXCL8 secretion); soluble CEACAM6 reduces C. albicans-induced CXCL8 secretion in CEACAM1-competent cells. Direct binding assay with C. albicans and recombinant CEACAM extracellular domains, shRNA knockdown of CEACAM1, CXCL8 ELISA, CEACAM1 phospho-tyrosine immunoblotting mBio High 28292985
2021 CEACAM6 on tumor cells suppresses anti-tumor T cell activity by interacting with CEACAM1 expressed on activated tumor-specific T cells; blocking CEACAM6-CEACAM1 interaction with the humanized antibody BAY 1834942 increases cytokine secretion by T cells and T cell-mediated cancer cell killing. T cell-cancer cell co-culture experiments, CEACAM6-blocking antibody (BAY 1834942), cytokine secretion assays, comparison with anti-PD-1/PD-L1/TIM-3 antibodies Oncoimmunology High 35141051
2022 CEACAM6 homophilic interactions in the cancer cell membrane activate the Src-FAK signaling pathway and inhibit anoikis in lung adenocarcinoma; treatment with exogenous CEACAM6 protein induced homophilic interactions and Src-FAK activation. CellphoneDB single-cell RNA-seq analysis, CEACAM6 protein treatment, immunoblotting for Src-FAK pathway, anoikis assays, ELISA and immunoblotting of cell culture conditioned media Translational oncology Medium 35358791
2015 CEACAM6 promotes cell proliferation in pancreatic carcinoma through regulation of cyclin D1 and CDK4 protein levels; CEACAM6 knockdown decreases cyclin D1 and CDK4, while overexpression increases them. siRNA knockdown and forced overexpression in pancreatic cell lines, immunoblotting for cyclin D1/CDK4, proliferation assays in vitro and xenograft in vivo Oncology reports Medium 26497080
2019 CRISPR/Cas9 knockout of CEACAM6 in PDA cells alters ECM-cell adhesion, catabolism, immune environment, transmembrane transport, and autophagy pathways; CEACAM6 loss increases mitochondrial basal and maximal respiratory capacity, indicating a role in bioenergetic regulation. CRISPR/Cas9 KO, quantitative proteomics, mitochondrial bioenergetics (Seahorse assay), xenograft tumor growth Scientific reports High 31797958
2023 CEACAM6 protein stability is enhanced through lysine lactylation downstream of ALDOB-mediated lactagenesis; the ALDOB/PDK1/lactate/CEACAM6 axis controls CRC cell proliferation and chemoresistance via the Warburg effect. Cell-based assays, lactylation inhibition, PDK1 activation studies, gene silencing of ALDOB and CEACAM6, chemoresistance assays Cell death & disease Medium 37816733
2021 CD151 associates physically with CEACAM6 (confirmed by pulldown and immunofluorescence co-localization), and CD151 silencing downregulates CEACAM6 and TGFβ1 both in vitro and in vivo, placing CEACAM6 downstream of a CD151/TGFβ1 axis in colorectal cancer. Co-immunoprecipitation, mass spectrometry, pulldown assay, immunofluorescence, RNA-seq after CD151 knockdown, xenograft International journal of biological sciences Medium 33767593
2023 CEACAM6 acts as a negative regulator of HO-1-mediated antioxidant defense in human alveolar type 2 epithelial cells (hAEC2s); epithelium-specific CEACAM6 overexpression (via AAV) increases nitrosative/oxidative stress and cell death upon cigarette smoke extract treatment in human precision-cut lung slices. CSE-resistant cell line model, transcriptomics, AAV-mediated CEACAM6 overexpression in human precision-cut lung slices, HO-1 inhibition, 3-nitrotyrosine measurement American journal of respiratory and critical care medicine Medium 37219322

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 447 17525800
2007 Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC cancer 203 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
1990 Characterization of a cDNA clone encoding a new species of the nonspecific cross-reacting antigen (NCA), a member of the CEA gene family. Biochemical and biophysical research communications 64 2306228
2004 CEACAM6 is a determinant of pancreatic adenocarcinoma cellular invasiveness. British journal of cancer 63 15316565
2014 CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway. PloS one 62 25398131
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 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
2023 Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect. Cell death & disease 48 37816733
2018 Advances and Biomedical Applications of Polypeptide Hydrogels Derived from α-Amino Acid N-Carboxyanhydride (NCA) Polymerizations. Advanced healthcare materials 47 29869375
2007 CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling. Oncogene 47 17653079
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 46 11590190
2019 Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target. Scientific reports 45 31797958
2024 The emerging roles of CEACAM6 in human cancer (Review). International journal of oncology 44 38240103
1983 Immunohistochemical localization of carcinoembryonic antigen (CEA), CEA-S, and nonspecific cross-reacting antigen (NCA) in carcinomas of lung. Cancer 42 6311398
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
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 40 28892050
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 38 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
1989 Carcinoembryonic antigen gene family: molecular cloning of cDNA for a PS beta G/FL-NCA glycoprotein with a novel domain arrangement. Biochemical and biophysical research communications 38 2735907
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
2014 Diet-induced hypoxia responsive element demethylation increases CEACAM6 expression, favouring Crohn's disease-associated Escherichia coli colonisation. Gut 36 24898815
2004 Overexpression of CEACAM6 promotes insulin-like growth factor I-induced pancreatic adenocarcinoma cellular invasiveness. Oncogene 36 15208677
2005 Myeloid antigens in childhood lymphoblastic leukemia: clinical data point to regulation of CD66c distinct from other myeloid antigens. BMC cancer 33 15826304
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
1985 Non-specific cross-reacting antigen (NCA) in individual maturation stages of myelocytic cell series. British journal of cancer 32 3882113
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
2017 Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells. mBio 31 28292985
2015 Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity. Biomaterials 31 26204223
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
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) 29 22918079
1983 Minor serine tRNA containing anticodon NCA (C4 RNA) from human and mouse cells. Biochemistry international 29 6435631
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
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
2024 Delivery of a BET protein degrader via a CEACAM6-targeted antibody-drug conjugate inhibits tumour growth in pancreatic cancer models. Nature communications 23 38467634
2021 Comprehensive RNA analysis of CSF reveals a role for CEACAM6 in lung cancer leptomeningeal metastases. NPJ precision oncology 23 34625644
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
2013 Significance of CD66c expression in childhood acute lymphoblastic leukemia. Leukemia research 22 24231528
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
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
1991 The putative role of members of the CEA-gene family (CEA, NCA an BGP) as ligands for the bacterial colonization of different human epithelial tissues. Zentralblatt fur Bakteriologie : international journal of medical microbiology 21 1718301
2017 The NCA-1 and NCA-2 Ion Channels Function Downstream of Gq and Rho To Regulate Locomotion in Caenorhabditis elegans. Genetics 20 28325749
2017 Dopamine negatively modulates the NCA ion channels in C. elegans. PLoS genetics 20 28968387
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
2023 CEACAM6 as a Novel Therapeutic Target to Boost HO-1-mediated Antioxidant Defense in COPD. American journal of respiratory and critical care medicine 18 37219322
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
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
1997 The 95-kilodalton membrane glycoprotein overexpressed in novel multidrug-resistant breast cancer cells is NCA, the nonspecific cross-reacting antigen of carcinoembryonic antigen. Cancer research 17 9407950
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
1989 Assignment of the coding sequence for carcinoembryonic antigen (CEA) and normal cross-reacting antigen (NCA) to human chromosome 19q13. Annals of human genetics 17 2596823
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
2022 CEACAM6 serves as a biomarker for leptomeningeal metastasis in lung adenocarcinoma. Cancer medicine 15 36082960
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
2018 CEACAM6 is associated with osteosarcoma metastasis and facilitates epithelial-mesenchymal transition in osteosarcoma cells. OncoTargets and therapy 14 29881289
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
2010 Aberrantly expressed CEACAM6 is involved in the signaling leading to apoptosis of acute lymphoblastic leukemia cells. Experimental hematology 14 20380867