Affinage

MUC16

Mucin-16 · UniProt Q8WXI7

Length
14507 aa
Mass
1519.2 kDa
Annotated
2026-04-29
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUC16 is a giant transmembrane mucin that serves as a dominant physical barrier on epithelial surfaces and functions as a multifaceted signaling hub in cancer progression and immune evasion. Its extracellular domain mediates heterotypic cell adhesion through direct binding to mesothelin (via a 64-amino acid region requiring tyrosine 318) and galectin-1 (via O-linked β-galactose chains), while its cytoplasmic tail links to the actin cytoskeleton through ERM proteins to maintain epithelial barrier integrity, tight junctions, and resistance to bacterial adherence (PMID:14676194, PMID:12615972, PMID:17898272, PMID:24968021). Proteolytic shedding by MT1-MMP releases the CA125 ectodomain, while a retained C-terminal fragment drives oncogenic signaling through JAK2/STAT3, Wnt/β-catenin, mTOR/c-Myc, and integrin/FAK pathways, promoting proliferation, glycolytic metabolic reprogramming, invasion, and metastasis in multiple cancer types (PMID:25205731, PMID:27167110, PMID:28196872, PMID:26046375, PMID:35628269, PMID:36271032). Shed MUC16 suppresses innate immunity by transcriptionally repressing NK cell cytotoxicity genes and engaging Siglec-9 on neutrophils to induce immunosuppressive phenotypes including PD-L1 and IDO1 upregulation (PMID:30626487, PMID:35396222, PMID:37644468).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 High

    Identifying MUC16's binding partners established it as a cell-adhesion mediator rather than merely a passive mucin barrier, revealing that CA125/MUC16 directly binds mesothelin to mediate ovarian cancer–mesothelial cell adhesion and binds galectin-1 through O-linked β-galactose chains.

    Evidence Expression cloning, Co-IP, flow cytometry adhesion assays with antibody blockade (mesothelin); MS identification with glycan-specific binding assays (galectin-1)

    PMID:12615972 PMID:14676194

    Open questions at the time
    • Cleavage site releasing CA125 ectodomain not yet mapped
    • Structural basis of MUC16–mesothelin interaction not resolved
    • In vivo significance of galectin-1 interaction not tested
  2. 2007 High

    MUC16 was shown to function as a dominant anti-adhesive barrier on uterine and corneal epithelial surfaces, resolving how the mucin glycocalyx contributes to epithelial protection at a molecular level.

    Evidence siRNA knockdown in uterine epithelial cells increasing trophoblast adhesion; RNAi in corneal epithelial cells reducing barrier function via dye exclusion and bacterial binding assays; peptide pull-down identifying ERM protein interaction with cytoplasmic tail

    PMID:17898272 PMID:17942799

    Open questions at the time
    • Mechanism of MUC16 removal from uterodomes during implantation window unknown
    • Whether ERM linkage is required for barrier function not directly tested
  3. 2008 High

    Mapping the minimal mesothelin-binding region to 64 amino acids (residues 296–359) with critical dependence on tyrosine 318 provided the first molecular resolution of the MUC16–mesothelin adhesion interface.

    Evidence Truncation mutagenesis and alanine scanning with quantitative ELISA, Western blot overlay, and flow cytometry on cancer cells

    PMID:19075018

    Open questions at the time
    • Reciprocal mapping of the binding site on MUC16 not performed
    • Crystal structure of the complex not determined
  4. 2009 High

    Muc16 knockout mice revealed that MUC16 is dispensable for normal development and fertility, redirecting attention to its context-dependent roles in disease rather than essential housekeeping function.

    Evidence Gene targeting (exon 3 deletion with lacZ reporter) in mice, comprehensive histological and fertility analysis

    PMID:19262696

    Open questions at the time
    • Pathogen challenge and wound-healing phenotypes not assessed in initial characterization
    • Compensatory mucin upregulation beyond Muc1 not explored
  5. 2014 High

    Two advances established MUC16's dual role as a barrier determinant and a substrate for proteolytic shedding: comprehensive knockdown studies confirmed MUC16 as the dominant epithelial barrier mucin (over MUC1), while identification of MT1-MMP as the sheddase revealed how CA125 is released and how shedding switches cells from adhesive to invasive behavior.

    Evidence Stable shRNA knockdown with multiple barrier readouts (dye, bacteria, transepithelial resistance, tight junctions); MT1-MMP overexpression with catalytic-dead mutant control, peritoneal explant adhesion, and invasion assays

    PMID:24968021 PMID:25205731

    Open questions at the time
    • Exact cleavage site within MUC16 not identified
    • Whether other MMPs contribute to shedding in vivo not resolved
    • Fate of the retained C-terminal fragment after shedding not characterized
  6. 2014 Medium

    Muc16-null mice showed activated Stat3/IL-6 signaling, increased corneal epithelial proliferation, and accelerated wound healing, establishing that MUC16 restrains inflammatory signaling in the ocular surface.

    Evidence Muc16-knockout mice with immunohistochemistry for phospho-STAT3, IL-6, BrdU proliferation, and corneal wound healing measurement

    PMID:24812549

    Open questions at the time
    • Whether STAT3 activation is cell-autonomous or secondary to barrier loss not distinguished
    • Findings limited to ocular surface; relevance to other epithelia untested
  7. 2015 Medium

    Connecting MUC16 to metabolic reprogramming via the mTOR/c-Myc axis in pancreatic cancer established that MUC16 is not merely an adhesion molecule but also controls glycolysis and nucleotide metabolism.

    Evidence shRNA knockdown with c-MYC overexpression rescue, glucose uptake and lactate secretion assays, LC-MS/MS metabolomics in pancreatic cancer cells

    PMID:26046375

    Open questions at the time
    • Direct molecular link between MUC16 and mTOR activation not identified
    • Metabolic reprogramming not validated in vivo
  8. 2016 Medium

    Discovery that the MUC16 C-terminal fragment (MUC16C) binds β-catenin and facilitates its nuclear translocation revealed a direct mechanism by which retained MUC16 activates Wnt signaling after ectodomain shedding.

    Evidence Co-IP with domain mapping, nuclear fractionation, Wnt reporter assays, MUC16 knockdown, and xenograft tumor model

    PMID:27167110

    Open questions at the time
    • Whether MUC16C–β-catenin interaction requires prior shedding not tested
    • Structural basis of the interaction not resolved
  9. 2017 Medium

    Multiple studies converged to define MUC16 as a signaling platform whose activity depends on specific glycosylation: MGAT5-dependent N-glycosylation was required for galectin-3/growth-factor-receptor engagement on lipid rafts, the C-terminal domain activated JAK2/STAT3 to drive drug resistance, and oncogenic KRAS was shown to transcriptionally upregulate MUC16 via ERK/c-Myc, establishing a feed-forward loop.

    Evidence MGAT5 loss-of-function with glycan-specific antibodies, lipid raft fractionation, and xenograft model; JAK2/STAT3 inhibitor rescue with cisplatin/gemcitabine resistance assays; c-Myc ChIP on MUC16 promoter with ERK inhibitor epistasis

    PMID:28108627 PMID:28196872 PMID:28617578

    Open questions at the time
    • Identity of specific growth factor receptors engaged via galectin-3 lattice incompletely defined
    • Whether KRAS–MUC16 feed-forward loop operates in non-pancreatic cancers unknown
    • Relative contributions of N- versus O-glycosylation to signaling not systematically compared
  10. 2019 High

    Functional immune assays demonstrated that MUC16 suppresses NK cell and macrophage cytotoxicity against ovarian cancer, directly linking ectodomain expression to immune evasion and in vivo survival advantage.

    Evidence NK and macrophage cytolysis assays, doublet formation assays, in vivo mouse survival with MUC16-knockdown tumors showing >2-fold increased survival

    PMID:30626487

    Open questions at the time
    • Receptor on NK cells mediating MUC16 recognition not identified in this study
    • Contribution of shed versus membrane-bound MUC16 to immune suppression not separated
  11. 2020 Medium

    MUC16 was connected to additional signaling partners: aberrant glycoforms enhance MUC16–ErbB receptor interaction to activate AKT/GSK3β in pancreatic cancer, while the C-terminal domain binds aldolase C to stabilize ALDOC protein and activate AMPK-driven glycolysis in gallbladder carcinoma.

    Evidence Co-IP of MUC16 with ErbB receptors and anti-MUC16 mAb blockade in xenografts; MS-identified MUC16c–ALDOC interaction with ALDOC knockdown rescue and glycolysis assays

    PMID:32502493 PMID:33359791

    Open questions at the time
    • Which specific ErbB family members are primary MUC16 partners not resolved
    • ALDOC interaction validated only in gallbladder cancer context
    • Whether glycoform-dependent signaling differences are tissue-specific not established
  12. 2022 High

    Genetic mouse models and integrin studies provided the strongest in vivo evidence for MUC16's pro-metastatic role: Muc16 deletion in KRAS-driven pancreatic cancer mice significantly reduced tumor progression and metastasis by downregulating cytoskeletal effectors, while truncated O-glycan-bearing MUC16 was shown to activate integrin/FAK signaling to promote migration, and shed CA125 was found to transcriptionally suppress NK cell cytotoxicity genes.

    Evidence KPCM/KCM genetically engineered mouse models with survival analysis and RNA-seq; CRISPR MUC16 KO with integrin Co-IP and FAK/ILK phosphorylation; RNA-seq of NK cells treated with CA125-enriched fractions from patient ascites

    PMID:35396222 PMID:35628269 PMID:36271032

    Open questions at the time
    • Cytoskeletal effectors (Actg2, Myh11, Pdlim3) validated only by knockdown — direct transcriptional regulation not shown
    • Whether integrin/FAK and immune-evasion mechanisms operate simultaneously in vivo not tested
    • NK cell receptor(s) engaged by shed CA125 not identified
  13. 2023 Medium

    Two studies extended MUC16's immune-suppressive and metastatic mechanisms: MUC16 engages Siglec-9 on neutrophils to induce PD-L1/IDO1-expressing immunosuppressive phenotypes, and the MUC16-Cter/HuR/c-Myc post-transcriptional axis drives triple-negative breast cancer lung metastasis.

    Evidence MUC16 protein stimulation of neutrophils with Siglec-9 analysis, RNA-seq, and NK functional assay; MUC16 shRNA/OE with RNA immunoprecipitation for HuR–cMyc, tail-vein metastasis model, and HuR inhibitor treatment

    PMID:36918912 PMID:37644468

    Open questions at the time
    • Direct Siglec-9 blockade/knockout not performed to confirm requirement
    • HuR/c-Myc axis not validated in cancer types beyond TNBC
    • Whether Siglec-9 engagement requires specific glycoforms of MUC16 not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the precise MUC16 cleavage site for MT1-MMP, the structural basis of MUC16–mesothelin and MUC16–β-catenin interactions, how membrane-bound versus shed MUC16 differentially contribute to immune suppression versus oncogenic signaling in vivo, and whether the diverse downstream pathways represent tissue-specific or universal MUC16 functions.
  • No structural (crystallographic or cryo-EM) data exist for any MUC16 interaction
  • Relative contribution of each signaling pathway in genetically defined in vivo models not established
  • Cleavage site for MT1-MMP-mediated shedding not mapped at amino acid resolution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 3 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 6 GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1643685 Disease 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-168256 Immune System 3
Partners
ALDOCCTNNB1ELAVL1EZRITGB1LGALS1LGALS3MSLN

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 CA125/MUC16 binds to mesothelin, a GPI-anchored cell surface molecule, mediating heterotypic cell adhesion between ovarian cancer cells and mesothelial cells; anti-mesothelin antibody blocks this binding and cell attachment. Expression cloning, flow cytometry, immunoprecipitation, cell adhesion assay with antibody blockade The Journal of biological chemistry High 14676194
2008 MUC16 cytoplasmic tail binds the N-terminus of ERM (ezrin/radixin/moesin) actin-binding proteins, linking MUC16 to the actin cytoskeleton; MUC16 knockdown in corneal epithelial cells reduces barrier function (increased dye penetrance) and increases Staphylococcus aureus binding. Cytoplasmic tail peptide pull-down of ERM proteins, RNA interference knockdown, rose bengal dye exclusion assay, bacterial binding assay, scanning and immunoelectron microscopy Investigative ophthalmology & visual science High 17898272
2008 A 64-amino acid region (residues 296–359) at the N-terminal of cell-surface mesothelin is the minimum fragment sufficient for binding CA125/MUC16; tyrosine 318 substitution with alanine abolishes CA125 binding, and partial loss is caused by mutations at tryptophan 321 and glutamic acid 324. Truncated mutagenesis, alanine replacement, Western blot overlay assay, ELISA, flow cytometry on cancer cells The Journal of biological chemistry High 19075018
2003 CA125/MUC16 is a counter receptor for galectin-1; soluble and membrane-associated CA125 fragments bind galectin-1 specifically via beta-galactose-terminated O-linked oligosaccharide chains, with preference for galectin-1 over galectin-3, and CA125 expression enhances galectin-1 presentation on the cell surface. Mass spectrometry, immunological analysis, binding specificity assays with glycan inhibitors, FACS-based non-conventional secretion reconstitution assay Journal of cell science High 12615972
2007 MUC16 is lost from uterodome (pinopode) surfaces during the receptive phase of the uterine cycle (LH+6 to LH+8); siRNA knockdown of MUC16 (but not MUC1) in ECC-1 uterine epithelial cells increased trophoblast cell adhesion, demonstrating MUC16 acts as a barrier to trophoblast adherence. Immunofluorescence microscopy on uterine biopsies, siRNA knockdown, trophoblast adhesion assay Biology of reproduction High 17942799
2014 MUC16 knockdown in epithelial cells decreases all barrier functions tested (dye penetrance, bacterial adherence and invasion, transepithelial resistance, tight junction formation, and apical surface size), while MUC1 knockdown increases barrier to dye and bacteria; demonstrating MUC16 provides the dominant epithelial barrier. Stable shRNA knockdown of MUC16 and MUC1 independently, dye penetrance assay, bacterial invasion assay, transepithelial resistance measurement, tight junction immunostaining PloS one High 24968021
2014 MT1-MMP (MMP-14) mediates ectodomain shedding of MUC16/CA-125; overexpression of catalytically active MT1-MMP in OVCA433 cells causes loss of surface MUC16, while inactive E240A mutant does not; MUC16 shedding reduces adhesion to peritoneal tissue explants but enhances meso-mimetic invasion. MT1-MMP overexpression and catalytic mutant (E240A) experiments, surface MUC16 immunoreactivity, 3D meso-mimetic culture adhesion assay, ex vivo peritoneal explant adhesion assay, invasion assay Biological chemistry High 25205731
2016 The C-terminal fragment of MUC16 (MUC16C) interacts with β-catenin (requiring β-catenin's trans-activation domain); this interaction facilitates cytosol-to-nucleus translocation of β-catenin, activating Wnt/β-catenin signaling to promote cell proliferation and migration, and tumorigenesis in nude mice. Co-immunoprecipitation with endogenous proteins using self-made MUC16 monoclonal antibody, domain-mapping, nuclear fractionation, reporter assays, MUC16 knockdown, xenograft tumor model Oncotarget Medium 27167110
2017 The C-terminal domain of MUC16 activates JAK2/STAT3/glucocorticoid receptor (GR) signaling to upregulate TSPYL5 in lung cancer cells; STAT3 inhibition reduces GR and TSPYL5; MUC16 overexpression induces cisplatin and gemcitabine resistance by downregulating p53. Stable shRNA knockdown and MUC16-Cter overexpression, transcriptome analysis, rescue experiments, STAT3 inhibitor treatment, Western blot of signaling proteins, in vivo tumor growth assay Clinical cancer research Medium 28196872
2015 MUC16 knockdown in pancreatic cancer cells reduces mTOR activity and c-MYC expression; ectopic c-MYC restores the metabolic and physiological alterations caused by MUC16 knockdown, including reduced glucose uptake, lactate secretion, and motility. Metabolomics showed MUC16 promotes glycolytic and nucleotide metabolite pools. shRNA knockdown, c-MYC overexpression rescue, glucose uptake and lactate secretion assays, LC-MS/MS metabolomics, Western blot for mTOR activity Oncotarget Medium 26046375
2017 Oncogenic KRAS upregulates MUC16 expression and CA125 shedding via the ERK/c-Myc axis in pancreatic cancer; c-Myc binds to the MUC16 promoter to transcriptionally activate its expression. KRAS manipulation in vitro and in vivo, ERK inhibitor treatment, c-Myc ChIP on MUC16 promoter, correlation analyses Molecular cancer research Medium 28108627
2012 MUC16 and mesothelin are co-expressed and physically interact (co-immunoprecipitation) in pancreatic ductal adenocarcinoma; MUC16 shRNA knockdown and antibody blockade of MUC16-mesothelin binding inhibit invasion and migration of pancreatic cancer cells. Microarray, immunohistochemistry, co-immunoprecipitation from pancreatic cancer tissue, shRNA knockdown, antibody blockade, invasion and migration assays Cancer science High 22320398
2019 MUC16 suppresses human and murine NK cell cytolysis and NK-tumor conjugate formation; MUC16-knockdown OVCAR-3 cells show increased susceptibility to NK and macrophage killing; mice bearing MUC16-knockdown tumors show >2-fold increased survival. MUC16 also suppresses ADCC by murine splenocytes. Target cell cytolysis assays, doublet formation assays, in vivo mouse survival model with MUC16-knockdown cells, in vitro NK/macrophage cytotoxicity assays Gynecologic oncology High 30626487
2017 MUC16 oncogenic signaling through its C-terminal ectodomain requires MGAT5-dependent N-glycosylation at two specific asparagine sites; oncogenic effects depend on Galectin-3 and growth factor receptors colocalized on lipid rafts; N-glycosylation site-directed antibodies block Galectin-3-mediated MUC16 interactions and inhibit ovarian cancer cell invasion and in vivo xenograft growth. MGAT5 loss-of-function, synthetic MUC16 glycopeptide-based monoclonal antibodies, galectin-3 expression knockdown, lipid raft fractionation, in vitro invasion assay, in vivo xenograft model ACS chemical biology High 28617578
2020 MUC16 enhances pancreatic cancer tumor malignancy through activation of AKT and GSK3β oncogenic signaling; this occurs partly through increased interactions between MUC16 and EGF-type (ErbB) receptors, which are enhanced by aberrant glycoforms of MUC16. Anti-MUC16 mAb AR9.6 blocks oncogenic signaling and reduces tumor growth in vivo. Isoform analysis, AKT/GSK3β phosphorylation Western blot, co-immunoprecipitation of MUC16 with ErbB receptors, mAb AR9.6 treatment in vitro and in mouse xenograft model Molecular therapy Medium 33359791
2018 MUC16 is cleaved at a specific location releasing the CA125 extracellular domain; the cleaved MUC16 subunits remain non-covalently associated with each other on the ovarian cancer cell surface, as demonstrated using antibodies specific to the retained carboxy-terminal juxtamembrane fragment. Generation and characterization of carboxy-terminus-specific monoclonal antibodies, immunoprecipitation, immunohistochemistry on ovarian tumor tissue PloS one Medium 29708979
2019 MUC16 facilitates cervical cancer cell proliferation and invasion via activation of JAK2/STAT3 phosphorylation, which promotes cyclooxygenase-2 (COX-2) expression; JAK2/STAT3 inhibition attenuates MUC16-driven COX-2 upregulation. shRNA knockdown and MUC16 overexpression, Western blot of JAK2/STAT3 phosphorylation, COX-2 expression, JAK2/STAT3 pharmacological inhibition, proliferation and invasion assays Genes & genomics Medium 31736008
2021 MUC16 promotes fibrotic processes in idiopathic pulmonary fibrosis by collaborating with the TGF-β1 canonical pathway; MUC16 forms a protein complex with phospho-SMAD3 at the cell membrane after TGF-β1 stimulation, and siRNA-mediated MUC16 knockdown inhibits TGF-β1-induced SMAD3 phosphorylation, Smad Binding Element activation, and myofibroblast transformation. siRNA knockdown, immunoprecipitation of MUC16/p-SMAD3 complex, confocal immunofluorescence, SMAD3 phosphorylation assay, Smad Binding Element reporter, fibroblast proliferation and mesenchymal transformation assays International journal of molecular sciences Medium 34204432
2020 MUC16 C-terminal domain (MUC16c) binds aldolase C (ALDOC), identified by mass spectrometry; MUC16c binding to ALDOC promotes ALDOC protein stability, disrupts ALDOC's ability to sense glucose deficiency, and activates the AMPK pathway to increase gallbladder carcinoma cell proliferation and glycolysis. Mass spectrometry interactome, co-immunoprecipitation, ALDOC knockdown rescue, glucose uptake and glycolysis assays, AMPK pathway Western blot, IHC Experimental cell research Medium 32502493
2022 MUC16 promotes liver metastasis of pancreatic cancer by regulating Neuropilin-2 (NRP2) via JAK2/STAT1 signaling; NRP2 knockdown in MUC16-overexpressed cells decreases cell adhesion and migration; MUC16 also promotes endothelial/p-selectin binding and liver colonization in ex vivo and in vivo mouse models. MUC16 knockdown and MUC16-Cter ectopic overexpression, RNA-sequencing, JAK2/STAT1 pathway analysis, NRP2 knockdown rescue, ex vivo liver colonization, in vivo liver metastasis mouse model Molecular cancer research Medium 35533267
2022 Deletion of Muc16 in KRAS-driven and KRAS/p53 pancreatic cancer mouse models (KPCM, KCM) significantly decreases tumor progression and metastasis, and prolongs survival; MUC16 loss downregulates cytoskeletal proteins Actg2, Myh11, and Pdlim3, and knockdown of these genes reduces metastatic potential. Genetically engineered mouse models (KPC/KPCM), survival analysis, RNA-seq, syngeneic cell metastasis assays, organoid growth assay, cytoskeletal gene knockdown Oncogene High 36271032
2022 Truncated O-glycan (Tn and STn antigen)-bearing MUC16 interacts with α4β1 integrin complexes on pancreatic cancer cells; this interaction activates integrin-linked kinase and focal adhesion kinase (ILK/FAK) signaling and promotes tumor cell migration; CRISPR/Cas9 deletion of MUC16 or anti-MUC16 antibody reduces migration. CRISPR/Cas9 MUC16 deletion, co-immunoprecipitation of MUC16 with α4β1 integrins, FAK/ILK phosphorylation Western blot, migration assays, anti-MUC16 antibody blockade International journal of molecular sciences Medium 35628269
2023 MUC16 promotes triple-negative breast cancer lung metastasis through a MUC16/HuR/cMyc axis; MUC16-Cter activates HuR (ELAVL1), which post-transcriptionally upregulates cMyc; RNA immunoprecipitation confirmed cMyc as a HuR target; MUC16 depletion or HuR pharmacological inhibition reduces cMyc expression and TNBC cell migration. MUC16 shRNA knockdown and MUC16-Cter overexpression, RNA immunoprecipitation (RIP) for HuR-cMyc association, microarray, tail vein in vivo metastasis model, HuR inhibitor (MS-444, CMLD-2) treatment Breast cancer research Medium 36918912
2022 MUC16/CA125 shed from ovarian cancer tumors inhibits NK cell activation and cytotoxicity at the transcriptional level, suppressing expression of genes involved in NK cell activation and cytotoxicity pathways, as shown by RNA-sequencing of NK cells treated with ascites or CA125-enriched protein fractions. Fcγ receptor-mediated NK activation assay, RNA sequencing of NK cells from patient ascites and in vitro CA125-treated NK cells, CA125-enriched protein fraction preparation Journal of immunology Medium 35396222
2023 MUC16 acts on neutrophils via Siglec-9 receptor to induce an inflammatory and immunosuppressive phenotype; MUC16 protein stimulation of neutrophils upregulates TNFA signaling, IL6-related pathways, and immunosuppression factors (PD-L1, IDO1, HHLA2), and supernatant from MUC16-stimulated neutrophils decreases NK cytotoxicity in vitro. MUC16 protein stimulation of neutrophils, flow cytometry, qPCR, RNA-sequencing, NK cytotoxicity assay with conditioned supernatant, Siglec-9 expression analysis on neutrophils Journal of ovarian research Medium 37644468
2009 Targeted disruption of the Muc16 gene in mice (knockout) shows that Muc16 is dispensable for normal development, fertility, and organ histology; Muc16 null mice are viable and normal, with downregulation of Muc1 transcripts in the uterus. Gene targeting (deletion of exon 3 with lacZ reporter), histological analysis, RT-PCR for mucin gene expression, fertility assessment PloS one High 19262696
2014 Loss of Muc16 in knockout mice activates Stat3 signaling and upregulates IL-6 in the conjunctiva, affects JunB signaling, causes basal-like cell distribution in suprabasal corneal epithelium with increased proliferation, accelerates corneal epithelial wound healing, and increases myofibroblast appearance and macrophage invasion in stroma after epithelial repair. Muc16-null knockout mice, immunohistochemistry for phospho-Stat3/AP-1/IL-6/TNFα, BrdU proliferation labeling, corneal wound healing measurement, keratocyte phenotype assessment Investigative ophthalmology & visual science Medium 24812549

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. The Journal of biological chemistry 455 14676194
1998 CA 125: the past and the future. The International journal of biological markers 318 10228898
1986 Elevated serum concentrations of CA-125 in patients with advanced endometriosis. Fertility and sterility 313 3457709
2005 Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecologic oncology 272 16061277
2001 The CA 125 gene: an extracellular superstructure dominated by repeat sequences. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 232 11786729
2002 Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene. International journal of cancer 186 11920644
1986 The use of CA-125 in the diagnosis and management of endometriosis. Fertility and sterility 186 3465595
2007 Functions of MUC16 in corneal epithelial cells. Investigative ophthalmology & visual science 166 17898272
2008 A binding domain on mesothelin for CA125/MUC16. The Journal of biological chemistry 157 19075018
2003 The cancer antigen CA125 represents a novel counter receptor for galectin-1. Journal of cell science 127 12615972
2011 Pathobiological implications of MUC16 expression in pancreatic cancer. PloS one 110 22066010
2014 Comparison of the transmembrane mucins MUC1 and MUC16 in epithelial barrier function. PloS one 105 24968021
2012 Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma. Cancer science 101 22320398
2014 MUC16: molecular analysis and its functional implications in benign and malignant conditions. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 95 25002120
2017 MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53. Clinical cancer research : an official journal of the American Association for Cancer Research 87 28196872
2007 MUC16 is lost from the uterodome (pinopode) surface of the receptive human endometrium: in vitro evidence that MUC16 is a barrier to trophoblast adherence. Biology of reproduction 87 17942799
2015 Understanding the Unique Attributes of MUC16 (CA125): Potential Implications in Targeted Therapy. Cancer research 78 26527287
2008 Alterations of the ocular surface epithelial MUC16 and goblet cell MUC5AC in patients with atopic keratoconjunctivitis. Allergy 76 18782111
2020 Association of MUC16 Mutation With Response to Immune Checkpoint Inhibitors in Solid Tumors. JAMA network open 75 32845327
1993 What do we know about the origin of CA 125? European journal of obstetrics, gynecology, and reproductive biology 72 8365529
2008 Neutrophil-to-lymphocyte ratio as an adjunct to CA-125 for the diagnosis of endometriosis. Fertility and sterility 67 18555226
2004 CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients. Gynecologic oncology 66 15297171
2011 Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass. Journal of gynecologic oncology 65 22247801
1997 Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression. Histopathology 64 9023557
2015 MUC16-mediated activation of mTOR and c-Myc reprograms pancreatic cancer metabolism. Oncotarget 61 26046375
1991 CA-125 concentrations in malignant and nonmalignant disease. Clinical chemistry 61 1934471
1999 CA 125: fundamental and clinical aspects. Seminars in cancer biology 59 10202133
2012 Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type. Pathobiology : journal of immunopathology, molecular and cellular biology 58 22286058
2016 Functional Consequences of Differential O-glycosylation of MUC1, MUC4, and MUC16 (Downstream Effects on Signaling). Biomolecules 56 27483328
2008 MUC16 expression during embryogenesis, in adult tissues, and ovarian cancer in the mouse. Differentiation; research in biological diversity 54 18637025
2002 Tissue and serum CA125 expression in endometrial cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 53 12144685
2020 Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer. Molecular therapy : the journal of the American Society of Gene Therapy 52 33359791
2019 Molecularly imprinted polymer SPE sensor for analysis of CA-125 on serum. Analytica chimica acta 52 31472701
2017 Oncogenic KRAS Targets MUC16/CA125 in Pancreatic Ductal Adenocarcinoma. Molecular cancer research : MCR 48 28108627
1997 Modulation of CA-125 release by inflammatory cytokines in human peritoneal mesothelial and ovarian cancer cells. Anticancer research 48 9329618
2002 Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer. Endoscopy 47 12170412
2018 Comparison of CA125, HE4, and ROMA index for ovarian cancer diagnosis. Current problems in cancer 42 30017407
2017 Smartphone-based immunosensor for CA125 detection. Talanta 42 28213228
2014 Membrane-type I matrix metalloproteinase-dependent ectodomain shedding of mucin16/ CA-125 on ovarian cancer cells modulates adhesion and invasion of peritoneal mesothelium. Biological chemistry 42 25205731
2008 MUC16 expression in Sjogren's syndrome, KCS, and control subjects. Molecular vision 42 19122828
2022 The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer: A Magic Biomarker but with Adversity. Diagnostics (Basel, Switzerland) 41 36552994
2014 CEA, AFP, CA125, CA153 and CA199 in malignant pleural effusions predict the cause. Asian Pacific journal of cancer prevention : APJCP 41 24528057
2013 MicroRNA-200c modulates the expression of MUC4 and MUC16 by directly targeting their coding sequences in human pancreatic cancer. PloS one 41 24204560
2024 MUC1 and MUC16: critical for immune modulation in cancer therapeutics. Frontiers in immunology 38 38361923
2019 A biosensor for determination of the circulating biomarker CA125/MUC16 by Surface Plasmon Resonance Imaging. Talanta 38 31514860
2016 Evaluation of HE4, CA-125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) in the Preoperative Assessment of Patients with Adnexal Mass. Oman medical journal 38 27602187
2017 Peritoneal dissemination of ovarian cancer: role of MUC16-mesothelin interaction and implications for treatment. Expert review of anticancer therapy 36 29241375
1998 Peritoneum and tissues of the female reproductive tract as physiological sources of CA-125. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 9679738
2017 Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth. ACS chemical biology 34 28617578
2022 ImmunoPET of Ovarian and Pancreatic Cancer with AR9.6, a Novel MUC16-Targeted Therapeutic Antibody. Clinical cancer research : an official journal of the American Association for Cancer Research 33 34907079
2019 MUC16 facilitates cervical cancer progression via JAK2/STAT3 phosphorylation-mediated cyclooxygenase-2 expression. Genes & genomics 33 31736008
2016 C-terminus of MUC16 activates Wnt signaling pathway through its interaction with β-catenin to promote tumorigenesis and metastasis. Oncotarget 33 27167110
2007 Regulation of MUC16 by inflammatory mediators in ocular surface epithelial cell lines. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 33 18342144
2012 Deciphering the molecular nature of ovarian cancer biomarker CA125. International journal of molecular sciences 32 22949880
2011 Tumour biomarkers in heart failure: is there a role for CA-125? European journal of heart failure 32 21525015
2015 Diagnostic performances of CA125, HE4, and ROMA index in ovarian cancer. European journal of gynaecological oncology 30 26390703
2009 CA125/MUC16 is dispensable for mouse development and reproduction. PloS one 30 19262696
2002 Use of CA-125 and ultrasound in high-risk women. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29 11860541
2018 Evaluation of HE4 and TTR for diagnosis of ovarian cancer: Comparison with CA-125. Journal of gynecology obstetrics and human reproduction 28 29609043
2020 MUC16 C-terminal binding with ALDOC disrupts the ability of ALDOC to sense glucose and promotes gallbladder carcinoma growth. Experimental cell research 27 32502493
2019 MUC16 suppresses human and murine innate immune responses. Gynecologic oncology 27 30626487
2014 Effects of the loss of conjunctival Muc16 on corneal epithelium and stroma in mice. Investigative ophthalmology & visual science 27 24812549
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