Affinage

MUC16

Mucin-16 · UniProt Q8WXI7

Length
14507 aa
Mass
1519.2 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUC16 (CA125) is a large transmembrane mucin composed of a serine/threonine-rich, heavily O-glycosylated amino-terminal domain, an extracellular domain dominated by tandem repeats containing the OC125/M11 epitopes, a transmembrane domain, and a short cytoplasmic tail, with shedding from the cell surface linked to phosphorylation and proteolytic cleavage (PMID:11786729). Beyond its biomarker role, MUC16 functions as an oncogenic driver: its membrane-proximal carboxy-terminal domain is both necessary and sufficient to promote tumor cell growth, soft-agar colony formation, invasion, EMT, and xenograft tumor formation, and these effects depend on the cytoplasmic tail and the extracellular ectodomain (PMID:21421261, PMID:25965947). In genetic mouse models of pancreatic cancer, Muc16 deletion slows Kras-driven tumor progression and metastasis and prolongs survival, establishing a causal role in carcinogenesis (PMID:36271032), while MUC16 itself is a transcriptional target of oncogenic KRAS/ERK signaling acting through c-Myc binding at its promoter (PMID:28108627). Oncogenic signaling by the ectodomain requires MGAT5-dependent N-glycosylation and is propagated through Galectin-3 and growth factor receptors clustered on lipid rafts to activate AKT and ERK (PMID:28617578, PMID:33580170), through ErbB receptor interactions driving AKT/GSK3β signaling (PMID:33359791), and through truncated O-glycan-bearing MUC16 binding α4β1 integrins to activate ILK/FAK (PMID:35628269); aberrant glycoforms strengthen these receptor interactions. MUC16 further engages JAK2/STAT signaling to drive metabolic reprogramming via mTOR/c-MYC (PMID:26046375), to control downstream effectors such as TSPYL5 and NRP2 that promote chemoresistance and liver metastasis (PMID:28196872, PMID:35533267), and protects cancer cells from TRAIL-induced apoptosis by downregulating DR5 and stabilizing cFLIP (PMID:24690311). It also suppresses innate immunity, inhibiting NK-cell and macrophage cytolysis (PMID:30626487), polarizing neutrophils toward an immunosuppressive phenotype via Siglec-9 (PMID:37644468), and driving IL-6-mediated regulatory T-cell differentiation (PMID:29337110). MUC16 secretion is constitutive and apically polarized in mesothelial cells and is markedly induced by inflammatory cytokines, ionizing radiation, and taxanes (PMID:8163699, PMID:8946867, PMID:9288793).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 Medium

    Established that CA125/MUC16 is constitutively and apically secreted by mesothelial cells and that this secretion is inducible by inflammatory stimuli, framing CA125 as a regulated, inflammation-responsive product rather than a passive surface marker.

    Evidence Polarized mesothelial monolayers on perforated membranes with IL-1β/TNF-α/LPS stimulation and immunoassay

    PMID:8163699

    Open questions at the time
    • Molecular machinery of polarized secretion not defined
    • Does not address tumor-cell shedding mechanism
  2. 1996 Medium

    Showed that ionizing radiation induces CA125 secretion in a cell-type-specific manner, implicating stress responses in regulation of MUC16 release.

    Evidence In vitro irradiation of mesothelial cells versus control cell types with supernatant CA125 measurement

    PMID:8946867

    Open questions at the time
    • Signal transduction linking radiation to secretion unresolved
    • p53 dependence only inferred from immunoreactivity
  3. 1997 Medium

    Demonstrated that taxanes actively induce de novo CA125 secretion dependent on protein/RNA synthesis, indicating drug-modulated MUC16 output rather than mere release of preformed protein.

    Evidence Taxane treatment of ovarian carcinoma lines with RIA, flow cytometry, and synthesis inhibitor co-treatment

    PMID:9288793

    Open questions at the time
    • Transcriptional pathway not mapped
    • Restricted to constitutively CA125-expressing lines
  4. 1998 Low

    Linked MUC16 shedding to phosphorylation and EGFR signaling, providing the first mechanistic handle on how surface CA125 is regulated and released.

    Evidence Biochemical phosphorylation assays of CA125 in cultured cells before and after release

    PMID:10228899

    Open questions at the time
    • Single-lab biochemical observation without mutagenesis of phospho-sites
    • Direct kinase and protease not identified
  5. 2001 Medium

    Defined the domain architecture of MUC16 (cytoplasmic tail, transmembrane domain, tandem-repeat ectodomain, O-glycosylated N-terminus), creating the structural framework for all later functional dissection.

    Evidence Gene cloning and sequence analysis of the CA125/MUC16 gene

    PMID:11786729

    Open questions at the time
    • Structural inferences from sequence only, no experimental structure
    • Cleavage site not directly demonstrated
  6. 2009 High

    Showed via knockout mice that MUC16 is dispensable for normal development and fertility, indicating its pathological importance lies in cancer rather than essential physiology.

    Evidence Targeted Muc16 knockout mouse with histology and Muc1 RT-PCR

    PMID:19262696

    Open questions at the time
    • Does not address tumor phenotypes
    • Compensation by other mucins not excluded beyond Muc1
  7. 2011 High

    Identified the MUC16 cytoplasmic tail and C-terminal domain as the oncogenic module, with knockdown abolishing and ectopic CTD expression conferring growth, invasion, EMT, and tumorigenesis.

    Evidence Reciprocal knockdown and MUC16CTD overexpression (with cytoplasmic tail deletion) in ovarian lines, soft agar, xenografts, EMT markers; parallel silencing study across ovarian/breast lines

    PMID:21421261 PMID:21852110

    Open questions at the time
    • Downstream effectors of the tail not yet defined
    • Isoform-dependent divergent phenotypes not molecularly explained
  8. 2013 High

    Identified mesothelin as a binding partner of MUC16 that drives motility/invasion through p38-dependent MMP-7 induction, defining a ligand-receptor axis for MUC16 in invasion.

    Evidence MSLN-MUC16 interaction studies with MMP-7 depletion and p38 inhibition in pancreatic cells

    PMID:23694968

    Open questions at the time
    • Whether MSLN signals through the CTD specifically unclear
    • Direct binding interface not mapped
  9. 2014 High

    Established that MUC16 confers apoptosis resistance by downregulating DR5, blocking caspase-8 activation at the DISC, and stabilizing cFLIP, explaining a survival advantage in tumors.

    Evidence Reciprocal MUC16 knockdown/MUC16CTD overexpression with caspase assays, DISC analysis, cFLIP siRNA

    PMID:24690311

    Open questions at the time
    • Mechanism connecting CTD to DR5/cFLIP transcription not defined
    • Limited to ovarian lines
  10. 2015 High

    Narrowed the transforming activity to as few as 114 C-terminal residues acting through the ectodomain and activating AKT/ERK, and showed metabolic reprogramming via mTOR/c-MYC toward glycolysis.

    Evidence NIH/3T3 transformation with deletion mapping, transgenic mouse tumor frequency; metabolomics with c-MYC rescue in pancreatic cells

    PMID:25965947 PMID:26046375

    Open questions at the time
    • Direct receptor engaging the minimal ectodomain not defined in transformation assay
    • Link between AKT/ERK and mTOR/c-MYC steps not fully traced
  11. 2017 Medium

    Placed MUC16 within KRAS/ERK/c-Myc transcriptional control of its own promoter and demonstrated JAK2/STAT3-driven downstream programs (GR/TSPYL5) and chemoresistance, integrating MUC16 into oncogenic transcriptional circuits.

    Evidence ChIP of c-Myc at MUC16 promoter with KRAS/ERK manipulation; MUC16-Cter rescue with STAT3 inhibition and signaling/transcriptome readouts

    PMID:28108627 PMID:28196872

    Open questions at the time
    • How MUC16 CTD activates JAK2 upstream not defined
    • Positive feedback between MUC16 and KRAS signaling not fully quantified
  12. 2017 High

    Demonstrated that MUC16 oncogenic signaling requires MGAT5-dependent N-glycosylation at defined sites and proceeds through Galectin-3 plus growth factor receptors on lipid rafts, giving a glycan-dependent receptor-clustering mechanism.

    Evidence MGAT5 loss-of-function, Galectin-3 manipulation, glycopeptide site-directed antibodies, lipid raft colocalization, invasion and xenograft assays

    PMID:28617578

    Open questions at the time
    • Identity of the specific receptors clustered with Gal3 not fully enumerated
    • Stoichiometry of glycan-Gal3 interaction unresolved
  13. 2018 Medium

    Showed the released MUC16 C-terminus drives IL-6/PI3K-AKT signaling that promotes Treg differentiation via JAK2/STAT3, extending MUC16 function to adaptive immune evasion.

    Evidence CD4+ T-cell co-culture, JAK2 inhibitor AG-490, Foxp3/Treg flow cytometry, IHC

    PMID:29337110

    Open questions at the time
    • Receptor mediating MUC16c uptake/cytoplasmic release unclear
    • In vivo Treg dependence not isolated from other cytokines
  14. 2019 Medium

    Defined MUC16 as a suppressor of innate immunity, inhibiting NK and macrophage cytolysis and conjugate formation, with knockdown improving survival and ADCC susceptibility.

    Evidence NK cytolysis and conjugate assays, knockdown xenograft survival, splenocyte ADCC

    PMID:30626487

    Open questions at the time
    • Molecular receptor on NK cells not identified in this study
    • Whether ectodomain shedding or surface MUC16 mediates effect unclear
  15. 2020 High

    Identified ErbB receptors as direct MUC16 partners driving AKT/GSK3β signaling preferentially via aberrant glycoforms, and validated antibody (AR9.6) blockade of the interaction as anti-tumor therapy.

    Evidence Co-IP of MUC16 with ErbB receptors, AKT/GSK3β western blot, AR9.6 antibody xenograft efficacy; parallel ERO1L/IL-6R/NF-κB regulation of MUC16 secretion

    PMID:33056994 PMID:33359791

    Open questions at the time
    • Which ErbB family member dominates not resolved
    • Direct binding interface and glycan dependence structurally undefined
  16. 2021 Medium

    Validated Galectin-3 as a therapeutic node downstream of MUC16, with Gal3 silencing or carbohydrate-domain antibody blocking AKT/ERK activation, invasion, and metastasis.

    Evidence Gal3 siRNA and anti-Gal3 antibody 14D11 with AKT/ERK blots, invasion and in vivo tumor/metastasis assays

    PMID:33580170

    Open questions at the time
    • Direct MUC16-Gal3 binding affinity not quantified here
    • Receptor partners activating AKT/ERK not fully resolved
  17. 2022 High

    Provided definitive in vivo genetic evidence that Muc16 promotes Kras-driven pancreatic carcinogenesis and metastasis, and dissected glycoform-dependent integrin (α4β1/ILK/FAK) signaling and a JAK2/STAT1/NRP2 metastatic axis.

    Evidence Muc16 knockout in KC/KPC mice, organoids, RNA-seq; CRISPR deletion with α4β1 Co-IP and ILK/FAK readouts; RNA-seq with NRP2 rescue and liver colonization models

    PMID:35533267 PMID:35628269 PMID:36271032

    Open questions at the time
    • Relative contribution of integrin versus ErbB versus Gal3 axes in vivo not parsed
    • Cytoskeletal effectors (Actg2/Myh11/Pdlim3) regulation mechanism incomplete
  18. 2023 Medium

    Extended MUC16 oncogenic mechanisms to breast cancer via a HuR/c-Myc post-transcriptional axis and to immunosuppression via Siglec-9-mediated neutrophil polarization, broadening the tumor and immune contexts of MUC16 action.

    Evidence shRNA knockdown with RNA-IP of HuR-cMyc and HuR inhibitors in TNBC metastasis models; MUC16 stimulation of neutrophils with Siglec-9 identification, RNA-seq, and NK cytotoxicity assays

    PMID:36918912 PMID:37644468

    Open questions at the time
    • How MUC16 CTD regulates HuR mechanistically unclear
    • Whether Siglec-9 directly binds MUC16 glycans not biochemically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The proximal molecular events connecting MUC16's short cytoplasmic tail and shed C-terminus to the multiple downstream kinase cascades (ErbB, Gal3, integrin, JAK2) remain incompletely defined, as does the protease and structural basis of ectodomain cleavage.
  • Identity of the sheddase/protease not established
  • No experimental structure of CTD-receptor complexes
  • Hierarchy and crosstalk among parallel signaling axes unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 1 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ELAVL1ERBBITGA4LGALS3MSLNNRP2SIGLEC9

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MUC16 (CA125) protein structure was characterized by cloning: it contains a short cytoplasmic tail, a transmembrane domain, and a large extracellular domain dominated by ~60+ tandem repeat units of 156 amino acids each that encompass the OC125 and M11 antibody epitope-binding sites and disulfide-bridged cysteine loops. The amino-terminal domain is serine/threonine-rich and accounts for most O-glycosylation. Release from the cell surface is proposed to depend on cytoplasmic phosphorylation followed by proteolytic cleavage. Gene cloning and sequence analysis of the CA125/MUC16 gene Tumour biology Medium 11786729
1998 CA125 (MUC16) undergoes phosphorylation (at serine and/or threonine residues) prior to its release from cultured cells, and is dephosphorylated upon release, suggesting phosphorylation regulates shedding. CA125 release appears directly linked to the EGF receptor signal transduction pathway. Biochemical analysis of CA125 in cultured cells, phosphorylation assays The International journal of biological markers Low 10228899
1994 Human peritoneal mesothelial cells secrete CA125 (MUC16) in a polarized manner, preferentially from their apical surfaces regardless of the side of the inducing stimulus. CA125 secretion is constitutive and is significantly enhanced by inflammatory cytokines IL-1β, TNF-α, and E. coli LPS. Polarized mesothelial monolayer cultures on perforated membranes, cytokine stimulation, microparticle enzyme immunoassay Journal of clinical pathology Medium 8163699
2011 MUC16 knockdown in ovarian cancer cells (NIH:OVCAR3) prevented cell surface localization of MUC16, reduced long-term growth, caused >8-fold reduction in soft agar colony formation, and completely prevented subcutaneous tumor formation in nude mice. Conversely, ectopic expression of the MUC16 C-terminal domain (MUC16CTD) in SKOV3 cells enhanced tumor cell growth, colony formation, tumor growth and metastasis in SCID mice, increased cell motility and invasiveness, decreased E-cadherin and increased N-cadherin and vimentin (EMT markers). Deletion of the cytoplasmic tail from MUC16CTD abolished all oncogenic effects, demonstrating the cytoplasmic tail is required. Stable knockdown via ER-targeted anti-MUC16 scFv, ectopic expression of MUC16CTD constructs with/without cytoplasmic tail deletion, soft agar assay, xenograft mouse models, invasion/motility assays, western blot for EMT markers Gynecologic oncology High 21421261
2013 Binding of mesothelin (MSLN) to MUC16 (CA125) markedly enhances pancreatic cancer cell motility and invasion via selective induction of MMP-7 through a p38 MAPK-dependent pathway. Depletion of MMP-7 or inhibition of p38 activity abolishes MSLN-mediated motility and invasion. Bioengineering and molecular biology tools to study MSLN-MUC16 interaction, MMP-7 depletion, p38 inhibition, cell motility and invasion assays Scientific reports High 23694968
2014 MUC16 attenuates TRAIL-induced apoptosis in ovarian cancer cells through multiple mechanisms: (1) decreasing TRAIL receptor R2 (DR5) expression; (2) inhibiting pro-caspase-8 activation at the death-inducing signaling complex (DISC); (3) maintaining cFLIP mRNA levels and preventing cFLIP protein degradation. The MUC16 C-terminal domain (MUC16CTD) is sufficient to mediate these anti-apoptotic effects. Stable MUC16 knockdown via ER-targeted scFv in OVCAR3, ectopic MUC16CTD expression in SKOV3, caspase activity assays, DISC analysis, cFLIP siRNA, flow cytometry, western blot BMC cancer High 24690311
2015 The carboxy-terminal portion of MUC16 (as few as 114 amino acids) is sufficient to induce oncogenic transformation: it increases soft agar growth, promotes Matrigel invasion, increases tumor growth in nude mice, and activates AKT and ERK signaling pathways. Oncogenic effects are exclusively dependent on the extracellular ectodomain. MUC16c354 transgenic mice crossed with p53-deficient mice showed higher spontaneous tumor frequency than p53+/- alone. Transformation was associated with upregulation of IL-1β, MMP2, and MMP9. Stable transfection of NIH/3T3 fibroblasts with MUC16 C-terminal constructs, soft agar assay, Matrigel invasion, xenograft tumor growth, transgenic mouse model, gene expression analysis PloS one High 25965947
2017 MUC16 regulates TSPYL5 gene expression in lung cancer through the JAK2/STAT3/glucocorticoid receptor (GR) axis. MUC16-Cter overexpression in MUC16 knockdown cells restores JAK2 (Y1007/1008), STAT3 (Y705), and GR activation. Inhibition of STAT3 (Y705) decreases GR and TSPYL5 levels. Additionally, MUC16 overexpression induces cisplatin and gemcitabine resistance by downregulating p53. Stable shRNA knockdown, MUC16-Cter overexpression rescue, transcriptome analysis, STAT3 inhibition, western blot for signaling proteins, in vitro growth, migration, in vivo tumor growth assays, IHC Clinical cancer research Medium 28196872
2015 MUC16-mediated oncogenic signaling activates mTOR and downstream c-MYC, reprogramming pancreatic cancer cell metabolism toward aerobic glycolysis. MUC16 knockdown reduces glucose uptake, lactate secretion, and glycolytic/nucleotide metabolite pools. Ectopic c-MYC expression in MUC16 knockdown cells restores altered cellular physiology. Metabolic alterations correlate with MUC16 expression in primary tumor tissue. Stable MUC16 knockdown, ectopic c-MYC expression rescue, LC-MS/MS metabolomics, glucose uptake assays, migration/invasion assays Oncotarget Medium 26046375
2017 MUC16 expression in pancreatic ductal adenocarcinoma is a downstream target of oncogenic KRAS. The KRAS/ERK axis induces upregulation of MUC16 and shedding of CA125 via the effector c-Myc in pancreatic cancer cells. c-Myc directly binds the MUC16 promoter and transcriptionally activates its expression. Chromatin immunoprecipitation (c-Myc binding to MUC16 promoter), KRAS/ERK pathway manipulation, cell line and in vivo experiments Molecular cancer research Medium 28108627
2018 MUC16 C-terminal domain (MUC16c), upon EGF induction, is released into the cytoplasm and significantly increases IL-6 expression and secretion via the PI3K/AKT pathway. Tumor-derived IL-6 promotes Foxp3 expression and regulatory T cell (Treg) differentiation through JAK2/STAT3 pathway activation, which is inhibited by JAK2 inhibitor AG-490. This MUC16c/IL-6/JAK2/STAT3 axis leads to tumor-associated Treg enrichment in pancreatic cancer. CD4+ T cell co-culture with pancreatic cancer cells, JAK2 inhibitor treatment, flow cytometry for Foxp3/Treg markers, western blot, IHC of tumor tissues Cancer letters Medium 29337110
2017 MUC16 oncogenic signaling through its C-terminal extracellular ectodomain requires MGAT5-dependent N-glycosylation at two specific asparagine sites. Galectin-3 and growth factor receptors colocalize on lipid rafts and are required for MUC16-mediated oncogenic effects. N-glycosylation site-directed antibodies block Galectin-3-mediated MUC16 interactions with cell surface signaling molecules, inhibit ovarian cancer cell invasion, and directly block in vivo tumor growth. MGAT5 loss-of-function, Galectin-3 expression manipulation, synthetic MUC16 glycopeptide antibodies, lipid raft co-localization, Matrigel invasion, in vivo xenograft assays ACS chemical biology High 28617578
2019 MUC16 inhibits human NK cell cytolysis and NK cell-tumor conjugate formation. MUC16 knockdown in OVCAR-3 cells increases susceptibility to murine NK cell and macrophage cytolysis. MUC16-knockdown tumor-bearing mice show >2-fold increase in survival. MUC16 also increases susceptibility of cancer cells to ADCC by splenocytes when knocked down. MUC16 acts as a regulator of both human and murine innate immune responses. NK cell cytolysis assays, conjugate formation assays, MUC16 knockdown OVCAR-3 xenograft mouse survival, splenocyte ADCC assays, in vitro cytotoxicity with activated NK cells and macrophages Gynecologic oncology Medium 30626487
2019 MUC16 facilitates cervical cancer cell proliferation, invasion, and migration via JAK2/STAT3 phosphorylation-mediated cyclooxygenase-2 (COX-2) expression. MUC16 overexpression activates JAK2/STAT3 via phosphorylation, upregulating COX-2, while MUC16 knockdown reverses these effects. JAK2/STAT3 inhibition attenuates MUC16-mediated COX-2 regulation. shRNA knockdown, overexpression, western blot for JAK2/STAT3 phosphorylation and COX-2, proliferation, invasion and migration assays Genes & genomics Low 31736008
2020 MUC16 isoforms activate oncogenic AKT and GSK3β signaling in pancreatic cancer through increased interactions with EGF-type (ErbB) receptors; these interactions are enhanced for aberrant glycoforms of MUC16. Anti-MUC16 monoclonal antibody AR9.6 blocks MUC16-ErbB receptor interactions and reduces oncogenic signaling, tumor growth, and metastasis in PDAC tumor-bearing mice. Co-immunoprecipitation of MUC16 with ErbB receptors, western blot for AKT/GSK3β, antibody blockade experiments, xenograft mouse models with mAb AR9.6 ± gemcitabine Molecular therapy High 33359791
2020 ERO1L promotes CA125 (MUC16) secretion in lung cancer through the following mechanism: ERO1L facilitates IL-6R secretion by promoting disulfide bond formation; IL-6R binds IL-6 and activates the NF-κB signaling pathway; NF-κB binds the MUC16 promoter to induce MUC16 overexpression; the extracellular segment of MUC16 is cleaved to form CA125; and the MUC16 C-terminus promotes EMT and IL-6 release, forming a positive feedback loop. Antibody chip screening, NF-κB binding to MUC16 promoter (ChIP implied), disulfide bond analysis, ERO1L manipulation, cell secretion assays Cell death & disease Medium 33056994
2022 MUC16 promotes liver metastasis of pancreatic ductal adenocarcinoma by upregulating Neuropilin-2 (NRP2) via JAK2/STAT1 signaling. NRP2 knockdown in MUC16-overexpressed cells decreases cell adhesion and migration. MUC16 and its Cter domain expression is required for cell survival and colonization in a liver-mimicking ex vivo environment and enhances liver metastasis in in vivo mouse models. MUC16 also alters cytoskeletal proteins Actg2, Myh11, and Pdlim3. MUC16 knockdown/overexpression, RNA-sequencing, NRP2 knockdown rescue, cell adhesion/migration assays, ex vivo liver colonization model, in vivo metastasis mouse model, IHC/IFC Molecular cancer research Medium 35533267
2022 Muc16 deletion in KrasG12D/+ and KrasG12D/+;Trp53R172H/+ mouse models of pancreatic cancer significantly decreases tumor progression and prolongs survival. Muc16 knockout reduces tumor microenvironment factors and incidence of liver and lung metastasis. MUC16 alters expression of cytoskeletal proteins Actg2, Myh11, and Pdlim3, whose knockdown reduces metastatic potential. Genetically engineered mouse model with Muc16 knockout crossed onto KC and KPC backgrounds, RNA-seq, organoid growth assays, endothelial/P-selectin binding assays, syngeneic cell metastasis assays Oncogene High 36271032
2022 Truncated O-glycan (Tn and STn antigen)-bearing MUC16 promotes pancreatic cancer cell migration by activating integrin-linked kinase/focal adhesion kinase (ILK/FAK) signaling through interactions with α4β1 integrin complexes. This association is stronger for aberrant glycoforms of MUC16. CRISPR/Cas9-mediated MUC16 deletion decreases migration; anti-MUC16 antibody targeting reduces migratory cascades. CRISPR/Cas9 MUC16 deletion, Co-immunoprecipitation of MUC16 with α4β1 integrins, FAK/ILK western blot, migration assays, antibody blockade International journal of molecular sciences Medium 35628269
2023 MUC16 promotes triple-negative breast cancer lung metastasis through HuR (ELAVL1)/c-Myc axis. MUC16 knockdown decreases invasion, migration, colony formation, and lung metastasis in tail vein mouse models. MUC16 regulates HuR, which directly binds cMyc mRNA (identified by RNA immunoprecipitation). Pharmacological HuR inhibition (MS-444 and CMLD-2) reduces cMyc expression. MUC16-Cter or HuR overexpression drives migration through MUC16/HuR/cMyc axis. shRNA knockdown, tail vein metastasis mouse model, RNA immunoprecipitation, microarray, ectopic MUC16-Cter and HuR overexpression, HuR pharmacological inhibitors, cMyc western blot Breast cancer research Medium 36918912
2023 MUC16 acts on neutrophils via Siglec-9 (its receptor expressed on neutrophils), polarizing them toward an inflammatory and immunosuppressive phenotype characterized by increased CD11b+, CD66b+, ICAM-1+ markers, elevated MMP9, IL-8, IL-1β, TNF-α, and ROS, upregulation of immunosuppressive factors PD-L1, IDO1, and IL-6, and via secreted factors from MUC16-stimulated neutrophils, decreased NK cytotoxicity in vitro. MUC16 protein stimulation of neutrophils, flow cytometry, RNA-sequencing of MUC16-stimulated neutrophils, qPCR, NK cytotoxicity assay with conditioned medium, ovarian cancer organoid co-culture Journal of ovarian research Medium 37644468
2009 CA125/MUC16 (Muc16) is dispensable for mouse development and reproduction. Muc16 homozygous knockout mice are viable, fertile, and histologically normal up to 1 year. Downregulation of another mucin gene, Muc1, was detected in the Muc16 knockout uterus. Targeted gene disruption (knockout mouse), histological analysis, RT-PCR for Muc1 PloS one High 19262696
1996 Irradiated mesothelial cells produce elevated CA125 (MUC16) secretion up to 32-fold over non-irradiated controls, demonstrating that ionizing radiation induces CA125 secretion specifically in mesothelial cells. Normal fibroblasts, mammary epithelium, and a CA125-negative ovarian cell line did not produce CA125 under these conditions. In vitro irradiation (500 cGy) of isolated mesothelial cells and control cell types, CA125 measurement in culture supernatants, p53 immunoreactivity as positive control Gynecologic oncology Medium 8946867
1997 Paclitaxel and docetaxel (taxanes) directly induce CA125 (MUC16) secretion in constitutively CA125-expressing ovarian carcinoma cell lines (OVCAR-3, HOC-7, SKOV-6) in a manner dependent on intact protein and RNA biosynthesis. CA125 concentration increases only in supernatant medium, not on cell surface or cytosol. CA125-negative cell lines do not respond to taxane treatment by expressing CA125. Taxane treatment of ovarian carcinoma cell lines, RIA for secreted CA125, immuno-flow cytometry for surface CA125, protein synthesis inhibitor co-treatment Cancer research Medium 9288793
2011 MUC16 gene silencing in ovarian and breast cancer cells (MUC16-low+) induces caspase-dependent apoptosis, reduces colony formation, adhesion, migration, and invasiveness associated with reduced MMP-2 activation. In MUC16-high+ cell lines, silencing does not affect the non-motile, non-invasive phenotype, suggesting different MUC16 isoforms with divergent functions. Transient and stable shRNA knockdown, caspase activity assays, colony formation, cell adhesion, migration, invasion assays, MMP-2 activity measurement European journal of cancer Medium 21852110
2021 Galectin-3 (Gal3) silencing in MUC16-expressing breast and ovarian cancer cells inhibits tumor cell invasion in vitro and attenuates tumor growth in murine models. An inhibitory anti-Gal3 antibody (14D11) targeting the carbohydrate-binding domain blocks AKT and ERK1/2 phosphorylation in MUC16-expressing cancer cells, inhibits Matrigel invasion, prolongs survival in flank tumor models, and retards lung metastasis by MUC16-expressing breast cancer cells. Gal3 siRNA knockdown, murine anti-Gal3 antibody (14D11) treatment, AKT/ERK western blot, Matrigel invasion, in vivo flank tumor and lung metastasis models Scientific reports Medium 33580170

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 The CA 125 tumour-associated antigen: a review of the literature. Human reproduction (Oxford, England) 798 2651469
2014 MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress. Molecular cancer 388 24886523
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 314 3457709
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
2013 Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation. Scientific reports 192 23694968
1986 The use of CA-125 in the diagnosis and management of endometriosis. Fertility and sterility 187 3465595
2018 MUC16 as a novel target for cancer therapy. Expert opinion on therapeutic targets 175 29999426
2018 Association of MUC16 Mutation With Tumor Mutation Load and Outcomes in Patients With Gastric Cancer. JAMA oncology 173 30098163
2011 MUC16 (CA125) regulates epithelial ovarian cancer cell growth, tumorigenesis and metastasis. Gynecologic oncology 151 21421261
1994 CA 125 secretion by peritoneal mesothelial cells. Journal of clinical pathology 125 8163699
2011 Pathobiological implications of MUC16 expression in pancreatic cancer. PloS one 111 22066010
2002 Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer. Journal of the National Cancer Institute 107 12441325
1985 Ca 125 and Ca 19-9: two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk. European journal of biochemistry 97 3922759
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
1992 CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis. Fertility and sterility 95 1531465
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 89 28196872
2015 Understanding the Unique Attributes of MUC16 (CA125): Potential Implications in Targeted Therapy. Cancer research 79 26527287
2020 Association of MUC16 Mutation With Response to Immune Checkpoint Inhibitors in Solid Tumors. JAMA network open 76 32845327
1998 More than 15 years of CA 125: what is known about the antigen, its structure and its function. The International journal of biological markers 73 10228899
1993 What do we know about the origin of CA 125? European journal of obstetrics, gynecology, and reproductive biology 72 8365529
2016 The diagnostic value of serum HE4 and CA-125 and ROMA index in ovarian cancer. Biomedical reports 62 27347403
2015 MUC16-mediated activation of mTOR and c-Myc reprograms pancreatic cancer metabolism. Oncotarget 61 26046375
1998 Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome. Human reproduction (Oxford, England) 61 9853880
1999 CA 125: fundamental and clinical aspects. Seminars in cancer biology 59 10202133
2011 CA125 (MUC16) gene silencing suppresses growth properties of ovarian and breast cancer cells. European journal of cancer (Oxford, England : 1990) 58 21852110
2018 MUC16 C terminal-induced secretion of tumor-derived IL-6 contributes to tumor-associated Treg enrichment in pancreatic cancer. Cancer letters 57 29337110
2016 Functional Consequences of Differential O-glycosylation of MUC1, MUC4, and MUC16 (Downstream Effects on Signaling). Biomolecules 56 27483328
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 55 33359791
1995 Tumor antigens CA 19.9, CA 125, and CEA in carcinoma of the uterine cervix. Gynecologic oncology 55 7729735
2008 MUC16 expression during embryogenesis, in adult tissues, and ovarian cancer in the mouse. Differentiation; research in biological diversity 54 18637025
1986 Tumor-associated antigen Ca 125 before and during the treatment of ovarian carcinoma. Obstetrics and gynecology 54 3008051
2017 Oncogenic KRAS Targets MUC16/CA125 in Pancreatic Ductal Adenocarcinoma. Molecular cancer research : MCR 49 28108627
1997 Modulation of CA-125 release by inflammatory cytokines in human peritoneal mesothelial and ovarian cancer cells. Anticancer research 48 9329618
2024 MUC1 and MUC16: critical for immune modulation in cancer therapeutics. Frontiers in immunology 45 38361923
2022 The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer: A Magic Biomarker but with Adversity. Diagnostics (Basel, Switzerland) 45 36552994
2008 MUC16 expression in Sjogren's syndrome, KCS, and control subjects. Molecular vision 42 19122828
1989 Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential. Cancer research 42 2702650
2018 MUC16 overexpression induced by gene mutations promotes lung cancer cell growth and invasion. Oncotarget 41 29552305
2013 MicroRNA-200c modulates the expression of MUC4 and MUC16 by directly targeting their coding sequences in human pancreatic cancer. PloS one 41 24204560
2015 Expression of the Carboxy-Terminal Portion of MUC16/CA125 Induces Transformation and Tumor Invasion. PloS one 40 25965947
2014 Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis. Human reproduction (Oxford, England) 37 24939955
2020 ERO1L promotes IL6/sIL6R signaling and regulates MUC16 expression to promote CA125 secretion and the metastasis of lung cancer cells. Cell death & disease 36 33056994
2017 Peritoneal dissemination of ovarian cancer: role of MUC16-mesothelin interaction and implications for treatment. Expert review of anticancer therapy 36 29241375
2015 Differential Expression of MUC12, MUC16, and MUC20 in Patients with Active and Remission Ulcerative Colitis. Mediators of inflammation 36 26770020
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 34 34907079
2017 Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth. ACS chemical biology 34 28617578
2019 MUC16 facilitates cervical cancer progression via JAK2/STAT3 phosphorylation-mediated cyclooxygenase-2 expression. Genes & genomics 33 31736008
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
2011 Tumour biomarkers in heart failure: is there a role for CA-125? European journal of heart failure 32 21525015
2006 MMP-2 expression associates with CA 125 and clinical course in endometrial carcinoma. Gynecologic oncology 32 16996112
2021 Bispecific T-Cell Engaging Antibodies Against MUC16 Demonstrate Efficacy Against Ovarian Cancer in Monotherapy and in Combination With PD-1 and VEGF Inhibition. Frontiers in immunology 31 33936101
2014 MUC16 mucin (CA125) attenuates TRAIL-induced apoptosis by decreasing TRAIL receptor R2 expression and increasing c-FLIP expression. BMC cancer 31 24690311
2009 CA125/MUC16 is dispensable for mouse development and reproduction. PloS one 31 19262696
2022 CA-125 KELIM as a Potential Complementary Tool for Predicting Veliparib Benefit: An Exploratory Analysis From the VELIA/GOG-3005 Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29 35867965
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
1998 CA 125 in biological fluids. The International journal of biological markers 28 10228906
2022 MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion. Molecular cancer research : MCR 27 35533267
2019 MUC16 suppresses human and murine innate immune responses. Gynecologic oncology 27 30626487
2017 CA 19-9 and CA 125 as potential predictors of disease recurrence in resectable lung adenocarcinoma. PloS one 27 29049328
2009 CA-125 and CRP are elevated in preeclampsia. Hypertension in pregnancy 27 19437230
2007 MUC16 in the lacrimal apparatus. Histochemistry and cell biology 27 17211626
1993 Purification and characterization of the CA 125 tumor-associated antigen from human ascites. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 7684153
2023 MUC16 stimulates neutrophils to an inflammatory and immunosuppressive phenotype in ovarian cancer. Journal of ovarian research 26 37644468
2021 Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies. Scientific reports 26 33580170
2018 Standard and optimal cut-off values of serum ca-125, HE4 and ROMA in preoperative prediction of ovarian cancer in Vietnam. Gynecologic oncology reports 26 30109256
2014 Association of the neutrophil-to-lymphocyte ratio and CA 125 with the endometriosis score. Clinical and experimental reproductive medicine 26 25599037
2017 Concentrations of MUC16 and MUC5AC using three tear collection methods. Molecular vision 25 28761326
2023 MUC16 promotes triple-negative breast cancer lung metastasis by modulating RNA-binding protein ELAVL1/HUR. Breast cancer research : BCR 24 36918912
2017 CA-125 in Disease Progression and Treatment of Lymphangioleiomyomatosis. Chest 24 28576630
2023 In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer. Vaccine 23 36813666
2021 Evaluation of Serum Biomarker CEA and Ca-125 as Immunotherapy Response Predictors in Metastatic Non-small Cell Lung Cancer. Anticancer research 22 33517292
2020 High mutation load, immune-activated microenvironment, favorable outcome, and better immunotherapeutic efficacy in melanoma patients harboring MUC16/CA125 mutations. Aging 21 32491995
1998 CA 125 production and release by ovarian cancer cells in vitro. The International journal of biological markers 21 10228901
1992 Expression of CEA, CA-125 and SCC antigen by biological fluids associated with pregnancy. European journal of obstetrics, gynecology, and reproductive biology 21 1607061
2024 MUC16: clinical targets with great potential. Clinical and experimental medicine 20 38758220
2022 Muc16 depletion diminishes KRAS-induced tumorigenesis and metastasis by altering tumor microenvironment factors in pancreatic ductal adenocarcinoma. Oncogene 20 36271032
1989 Co-expression of CA 19-9, DU-PAN-2, CA 125, and TAG-72 in pancreatic adenocarcinoma. The American journal of surgical pathology 20 2699170
2016 Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors. Virchows Archiv : an international journal of pathology 19 27003157
2005 Introducing the MUC16 gene: implications for prevention and early detection in epithelial ovarian cancer. Biological research for nursing 19 15788735
2015 CA-125, but not galectin-3, complements CA 19-9 for discriminating ductal adenocarcinoma versus non-malignant pancreatic diseases. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 18 26613889
2010 Conflicting views on the molecular structure of the cancer antigen CA125/MUC16. Disease markers 18 20683153
2009 Premenarchal ovarian torsion and elevated CA-125. Journal of pediatric and adolescent gynecology 18 19589703
2018 The Biomarkers NT-proBNP and CA-125 are Elevated in Patients with Idiopathic Atrial Fibrillation. Journal of atrial fibrillation 17 31139280
1999 Serum CA 125 levels in children with non-Hodgkin's lymphoma. Pediatric hematology and oncology 17 10407867
1993 CA 125 and CA 19-9 immunolocalization in normal, hyperplastic, and carcinomatous endometrium. Cancer 16 8453578
1992 What do CA 125 and other antigens tell us about ovarian cancer biology? Acta obstetricia et gynecologica Scandinavica. Supplement 15 1502896
2020 Comparison of HE 4, CA 125, ROMA score and ultrasound score in the differential diagnosis of ovarian masses. Journal of gynecology obstetrics and human reproduction 14 32084612
2009 Expression and epitope characterization of a recombinant CA 125 repeat: fourth report from the ISOBM TD-1 workshop. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 14 19321947
2008 Differential expression of MUC16 in human oral mucosal epithelium and cultivated epithelial sheets. Experimental eye research 14 18644592
1995 Markers supplementing CA 125 in ovarian cancer. Annals of medicine 14 7741989
2024 Interrogating the Theranostic Capacity of a MUC16-Targeted Antibody for Ovarian Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 13 38485271
2022 Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling. International journal of molecular sciences 13 35628269
2000 CA-125 levels are related to the likelihood of pregnancy after in vitro fertilization and embryo transfer. American journal of reproductive immunology (New York, N.Y. : 1989) 13 10698036
1998 Regulation of CA 125 expression in cultured human carcinoma cells. The International journal of biological markers 13 10228902
1998 Immunohistochemistry of CA 125. Unusual expression in normal tissues, distribution in the human fetus and questions around its application in diagnostic pathology. The International journal of biological markers 13 10228903
1997 Paclitaxel- and docetaxel-dependent activation of CA-125 expression in human ovarian carcinoma cells. Cancer research 13 9288793
1996 Radiation-induced CA 125 production by mesothelial cells. Gynecologic oncology 13 8946867
2010 Serum concentrations of CA-125 in normal and preeclamptic pregnancies. Archives of gynecology and obstetrics 12 21046132

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