Affinage

MUC1

Mucin-1 · UniProt P15941

Length
1255 aa
Mass
122.1 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUC1 is a transmembrane mucin processed into two subunits whose membrane-tethered C-terminal subunit (MUC1-C) functions as a signal-transducing oncoprotein, while the cell-surface ectodomain provides a protective epithelial barrier (PMID:11133508, PMID:19118037). At the surface, MUC1 serves as an adhesion site for bacteria such as Pseudomonas aeruginosa and counter-regulates inflammatory responses, with knockout animals showing increased ocular and conjunctival infection and macrophage hyperactivation (PMID:11133508, PMID:10359313, PMID:26393683). MUC1-C is subject to sequential proteolytic processing: TACE/ADAM17 sheds the ectodomain to generate a membrane-bound C-terminal fragment that is then cleaved by presenilin-dependent gamma-secretase (PMID:19711367, PMID:26393683). Its cytoplasmic tail is a phosphorylation hub, tyrosine-phosphorylated by the Met receptor and by the Src-family kinase p56lck following T-cell receptor ligation, and serine/threonine-phosphorylated downstream of TGF-β1/SMAD3, with N-glycosylation at Asn-36 and palmitoylation at a CQC motif governing galectin-3-bridged EGFR association and Rab11-dependent endosomal recycling, respectively (PMID:17889671, PMID:18625714, PMID:16507569, PMID:15513966, PMID:31801904). Once activated, MUC1-C directly binds an array of transcriptional and signaling partners—ERα, JAK1/STAT3, TAK1/TRAF6, β-catenin/TCF4, BMI1, YAP/ZEB1, and p53—to drive target-gene programs including ERα-responsive genes, MYC, EGFR, CDA, and NF-κB-dependent transcription, frequently through autoinductive feedback loops (PMID:16427018, PMID:21325207, PMID:25659581, PMID:26907633, PMID:27893710, PMID:27658423, PMID:27092881). Through these circuits MUC1-C promotes epigenetic silencing of CDKN2A/p16INK4a via PRC1/BMI1, metabolic reprogramming toward glycolysis and nucleotide biosynthesis, and cancer stem-cell self-renewal and neuroendocrine lineage plasticity (PMID:27893710, PMID:32103170, PMID:19118037, PMID:28720669). In normal physiology MUC1 enhances HIF-1α-mediated protection of renal tubules during ischemia, while its expression is hormonally and developmentally controlled at the uterine surface during implantation (PMID:25925251, PMID:9421424). MUC1-C abundance is itself terminated by PPARγ-mediated ubiquitination at Lys134 (PMID:24292674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 1996 Medium

    Established that MUC1 is not exclusively membrane-bound, defining a secreted splice isoform detectable in cancer patient sera and broadening the protein's potential extracellular roles.

    Evidence Isoform-specific monoclonal antibodies and Western blotting of breast cancer secretions and patient sera

    PMID:8912645

    Open questions at the time
    • Functional role of the secreted isoform not defined
    • Relationship to the transmembrane signaling functions unclear
  2. 1998 Medium

    Resolved how MUC1 surface levels are regulated in reproduction, showing hormonal induction and local embryo-driven removal to permit implantation.

    Evidence Northern blot, immunofluorescence, and uterine epithelial/trophoblastic vesicle coculture in rabbit

    PMID:9421424

    Open questions at the time
    • Molecular nature of the blastocyst-derived signal not identified
    • Mechanism of local MUC1 removal undefined
  3. 1999 High

    Defined MUC1's protective barrier function in vivo, demonstrating that its loss predisposes epithelial surfaces to bacterial infection.

    Evidence Muc1 knockout mice with bacterial speciation of conjunctival infection

    PMID:10359313

    Open questions at the time
    • Molecular basis of anti-bacterial protection not dissected here
  4. 2001 High

    Identified the molecular basis of MUC1's barrier role by showing the ectodomain acts as a bacterial adhesion site.

    Evidence Muc1 transfection of CHO cells, bacterial adhesion assays, elastase cleavage and deletion mutants

    PMID:11133508

    Open questions at the time
    • Receptor/ligand pairing with bacterial adhesins not defined
    • Whether adhesion is protective or facilitates colonization not resolved
  5. 2004 High

    Showed the MUC1 cytoplasmic tail participates in immune signal transduction, linking it to TCR-proximal kinase activity.

    Evidence Co-IP with p56lck, membrane fractionation, siRNA with Ca2+ flux/ERK/CD69/IL-2 readouts in T cells

    PMID:15513966

    Open questions at the time
    • Direct kinase-substrate phosphorylation site on MUC1 not mapped
    • Whether p56lck phosphorylates MUC1 directly not shown
  6. 2006 High

    Established MUC1-C as a direct transcriptional cofactor by showing it stabilizes ERα and enhances estrogen-responsive transcription.

    Evidence Co-IP, ChIP, ubiquitination and reporter assays with 17β-estradiol stimulation

    PMID:16427018

    Open questions at the time
    • Whether nuclear MUC1-C requires prior cleavage not addressed
    • Generality across non-breast contexts unknown
  7. 2006 High

    Defined a post-translational control of MUC1 trafficking, showing palmitoylation at the CQC motif governs endosomal recycling.

    Evidence [3H]palmitate labeling, CQC mutagenesis, trafficking rate constants, Rab11 colocalization, AP-1 Co-IP

    PMID:16507569

    Open questions at the time
    • Palmitoyltransferase responsible not identified
    • Link between recycling and signaling output not established
  8. 2007 High

    Connected MUC1-C glycosylation to receptor signaling, showing Asn-36 N-glycosylation enables galectin-3-bridged MUC1–EGFR association.

    Evidence Glycosylation assays, Asn-36 mutagenesis, miR-322 suppression, reciprocal Co-IP

    PMID:17889671

    Open questions at the time
    • Structural basis of the galectin-3 bridge not resolved
  9. 2007 High

    Revealed a tumor-suppressive facet of the cytoplasmic tail by showing it sequesters β-catenin to restrain proliferative transcription.

    Evidence CD8/MUC1 fusion transfection, Co-IP, LEF-1 reporter, Muc1+/+ vs -/- proliferation

    PMID:17524503

    Open questions at the time
    • Reconciliation with later β-catenin/TCF4-driven MYC activation context-dependent and unresolved
  10. 2007 High

    Mapped a complete signaling cascade by which neutrophil elastase induces MUC1 transcription, distinguishing it from MUC5AC regulation.

    Evidence Inhibitors, dominant-negatives, RNAi, and reporter assays in lung epithelial cells

    PMID:17600314

    Open questions at the time
    • In vivo relevance of the PKCδ→Duox1→TACE→Sp1 axis not tested
  11. 2008 High

    Identified Met as a direct MUC1 cytoplasmic-tail kinase and linked HGF signaling to nuclear MUC1 and p53-dependent transcriptional output.

    Evidence In vitro kinase assay, live-cell nuclear imaging, ChIP/reporter at MMP1 promoter

    PMID:18625714

    Open questions at the time
    • How phosphorylation drives nuclear import mechanistically not defined
  12. 2009 High

    Completed the proteolytic processing model by demonstrating gamma-secretase cleaves the membrane-bound MUC1 C-terminal fragment after ectodomain shedding.

    Evidence Gamma-secretase and TACE inhibitors, nicastrin siRNA and Co-IP, cleavage-product Westerns

    PMID:19711367

    Open questions at the time
    • Fate and signaling role of the released intracellular fragment not defined
  13. 2009 High

    Pinpointed tandem cytoplasmic sequences mediating direct β-catenin and EGFR binding and validated them as druggable with a dominant-negative peptide.

    Evidence Peptide competition, Co-IP, EGFR degradation assay, xenograft and MMTV-pyVmT models

    PMID:19118037

    Open questions at the time
    • Structural detail of the binding interfaces not resolved
  14. 2011 High

    Showed MUC1-C is required for JAK1-driven STAT3 activation and forms an autoinductive transcriptional loop at its own promoter.

    Evidence Reciprocal Co-IP, ChIP, siRNA, GO-201 inhibitor

    PMID:21325207

    Open questions at the time
    • Whether MUC1-C directly enhances JAK1 catalytic activity not shown
  15. 2012 Medium

    Demonstrated context-dependence of the MUC1–c-Met axis, with MUC1 restraining HGF-induced c-Met activation and invasion in HCC.

    Evidence Co-IP, siRNA, c-Met inhibitor, migration/invasion assays in HCC cells

    PMID:22962849

    Open questions at the time
    • Single Co-IP without reciprocal validation in this system
    • Reconciliation with Met-driven pro-tumor MUC1 signaling elsewhere unresolved
  16. 2013 High

    Identified a mechanism terminating MUC1-C signaling, revealing PPARγ as an E3 ligase that ubiquitinates MUC1-C at Lys134 for degradation.

    Evidence Co-IP, ubiquitination assay, Lys134 mutagenesis, proteasome inhibitor, proliferation assay

    PMID:24292674

    Open questions at the time
    • Physiological signals controlling PPARγ ligase activity toward MUC1-C unknown
  17. 2015 High

    Linked MUC1-C to inflammatory NF-κB signaling via direct TAK1/TRAF6 binding in a positive feedback loop relevant to colon cancer.

    Evidence Co-IP, knockdown, NF-κB reporter, MUC1+/-/IL-10-/- mouse model

    PMID:25659581

    Open questions at the time
    • Whether MUC1-C enhances TAK1 kinase activity directly not shown
  18. 2015 High

    Defined a cytoprotective role in renal ischemia, showing MUC1 traffics to the nucleus and enhances HIF-1α stabilization and glycolytic gene induction.

    Evidence Immunofluorescence localization, Muc1 KO + IRI model, HIF-1α and AMPK measurements

    PMID:25925251

    Open questions at the time
    • Direct MUC1–HIF-1α interaction not demonstrated
    • Mechanism of HIF-1α stabilization unresolved
  19. 2016 High

    Established a MUC1-C/β-catenin/TCF4 transcriptional mechanism driving MYC in multiple myeloma.

    Evidence CRISPR silencing, ChIP, Co-IP, qRT-PCR, GO-203 inhibitor

    PMID:26907633

    Open questions at the time
    • Determinants of β-catenin promoter recruitment by MUC1-C not defined
  20. 2016 High

    Linked MUC1-C to PRC1-mediated epigenetic silencing of p16INK4a through MYC-dependent BMI1 induction and direct BMI1 binding.

    Evidence Co-IP, ChIP, miR-200c reporter, gene silencing, GO-203

    PMID:27893710

    Open questions at the time
    • Direct effect on H2A ubiquitylation not measured here
  21. 2016 High

    Connected MUC1-C to Hippo/YAP and WNT crosstalk by repressing CRB3 with ZEB1 and forming YAP/β-catenin complexes.

    Evidence ChIP, Co-IP, siRNA, promoter reporter, LATS1/2 phosphorylation analysis

    PMID:27658423

    Open questions at the time
    • Order of events between CRB3 repression and polarity loss not fully resolved
  22. 2016 High

    Showed MUC1 acts as a direct transcriptional activator of EGFR by binding its promoter in endometrial cancer.

    Evidence siRNA, CRISPR KO, ChIP at two EGFR promoter regions, qPCR/Western, proliferation

    PMID:27092881

    Open questions at the time
    • Cofactors required for MUC1 promoter occupancy not identified
  23. 2016 High

    Defined MUC1 as an anti-inflammatory counter-regulator of macrophage phagocytosis and cytokine output, predominantly in M1 macrophages.

    Evidence Muc1 KO macrophages, phagocytosis/ROS/TNF-α assays, TACE inhibitor

    PMID:26393683

    Open questions at the time
    • Downstream signaling restraining phagocytosis not mapped
  24. 2017 Medium

    Linked MUC1 to acquired chemoresistance via EGFR-driven ABCB1 upregulation.

    Evidence Gain/loss-of-function, EGFR/ABCB1 shRNA and inhibitors, xenografts

    PMID:28796259

    Open questions at the time
    • Pathway inferred from inhibitor experiments rather than direct binding
    • Direct MUC1 occupancy at ABCB1 not shown
  25. 2017 Medium

    Established MUC1-driven metabolic reprogramming as a basis for radiation resistance through elevated glycolysis and nucleotide pools.

    Evidence Knockdown/overexpression, metabolomics, γH2AX, 3-bromopyruvate rescue in vitro and in vivo

    PMID:28720669

    Open questions at the time
    • Transcriptional/enzymatic targets mediating glycolytic shift not all defined
  26. 2019 High

    Defined a TGF-β1/SMAD3 phosphorylation mechanism on MUC1-CT (Thr41/Tyr46) driving fibrosis, with galectin-3 providing a TGF-β-independent bridge.

    Evidence Phospho-specific analysis, Co-IP, nuclear fractionation, siRNA/GO-201, Muc1 KO + bleomycin model

    PMID:31801904

    Open questions at the time
    • Kinase directly phosphorylating Tyr46 downstream of SMAD3 not identified
  27. 2020 High

    Connected MUC1-C to pyrimidine metabolic reprogramming under ER stress by transcriptionally activating CDA for survival.

    Evidence ChIP at CDA promoter, CDA activity assay, transcriptomics/metabolomics, knockdown, inhibitors

    PMID:32103170

    Open questions at the time
    • Cofactors recruiting MUC1-C to the CDA promoter not defined
  28. 2020 High

    Established MUC1-C as a driver of lineage plasticity and stemness, suppressing AR and p53 while inducing pluripotency and neuroendocrine programs.

    Evidence siRNA, CRISPR, ChIP, sphere formation and tumorigenicity assays in prostate cancer

    PMID:31953400

    Open questions at the time
    • Hierarchy among the many induced factors not fully ordered
  29. 2022 Medium

    Identified YBX1 as a direct upstream transcriptional activator of MUC1 contributing to lung adenocarcinoma stemness and metastasis.

    Evidence ChIP, dual-luciferase reporter, YBX1 silencing/overexpression with MUC1 rescue, mouse models

    PMID:34976785

    Open questions at the time
    • Single-lab finding; broader generality of YBX1 control of MUC1 untested
  30. 2022 Medium

    Revealed a post-translational MUC1-C function stabilizing EGFRvIII against lysosomal degradation within an NF-κB feedback loop in glioblastoma.

    Evidence CRISPR screen, siRNA, lysosome colocalization, NF-κB inhibitor, Western blotting

    PMID:36516884

    Open questions at the time
    • Mechanism by which MUC1-C diverts EGFRvIII from lysosomes not defined
    • Mechanism partially inferred

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MUC1-C reconciles its context-dependent tumor-suppressive (β-catenin sequestration, c-Met restraint) versus oncogenic (β-catenin/TCF4-MYC, EGFR amplification) roles, and the structural basis of its many direct interactions, remain unresolved.
  • No structural model of MUC1-C interaction interfaces
  • Determinants switching MUC1-C between suppressive and oncogenic outputs unknown
  • Rules governing nuclear translocation versus membrane signaling undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005634 nucleus 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-4839726 Chromatin organization 1
Partners
BMI1CTNNB1EGFRESR1JAK1STAT3TAK1TCF4

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 MUC1-C (C-terminal subunit) is N-glycosylated at Asn-36, and this N-glycosylation is required for upregulation of galectin-3 expression. N-glycosylated MUC1-C increases galectin-3 mRNA levels by suppressing miR-322, thereby stabilizing galectin-3 transcripts. In turn, galectin-3 binds to MUC1-C at the glycosylated Asn-36 site and forms a bridge between MUC1 and EGFR, making galectin-3 essential for EGF-mediated MUC1–EGFR interaction. In vitro glycosylation assays, miRNA suppression experiments, co-immunoprecipitation, mutagenesis of Asn-36 Molecular cell High 17889671
2006 The MUC1 C-terminal subunit (MUC1-C) directly binds the ERα DNA-binding domain, stabilizes ERα by blocking its ubiquitination and proteasomal degradation, enhances ERα occupancy on estrogen-responsive promoters, and increases recruitment of p160 coactivators SRC-1 and GRIP1, thereby stimulating ERα-mediated transcription. The interaction is stimulated by 17β-estradiol. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), ubiquitination assay, transcription reporter assay Molecular cell High 16427018
2011 MUC1-C associates with the gp130–JAK1–STAT3 complex; the MUC1-C cytoplasmic domain directly interacts with JAK1 and STAT3, and MUC1-C is required for JAK1-mediated STAT3 activation. In turn, activated STAT3 and MUC1-C co-occupy the MUC1 promoter, forming an autoinductive loop that drives MUC1 transcription. Co-immunoprecipitation of endogenous proteins, ChIP, siRNA knockdown, inhibitor (GO-201) treatment Science signaling High 21325207
2015 MUC1-C binds directly to TAK1 and mediates association of TAK1 with TRAF6, activating NF-κB-mediated TAK1 transcription; in a positive feedback loop, TAK1-induced NF-κB signaling is further promoted by MUC1-C, linking MUC1-C to inflammatory NF-κB signaling in colon cancer. Co-immunoprecipitation, gene knockdown, NF-κB reporter assay, in vivo MUC1+/−/IL-10−/− mouse model Oncogene High 25659581
2008 The Met receptor tyrosine kinase directly phosphorylates tyrosine at the YHPM motif in the MUC1 cytoplasmic tail (MUC1CT). HGF stimulation facilitates nuclear localization of MUC1CT. Met-phosphorylated MUC1CT enhances interaction with p53 and suppresses AP-1 activity at the MMP1 promoter, reducing MMP1 transcription and HGF-induced invasiveness. Co-immunoprecipitation, in vitro kinase assay, real-time confocal imaging for nuclear localization, ChIP/promoter reporter assay, siRNA knockdown The Journal of biological chemistry High 18625714
2006 MUC1 is dually palmitoylated at a CQC motif at the boundary of the transmembrane and cytoplasmic domains. Palmitoylation is not required for MUC1 delivery to the cell surface or endocytosis but is required for recycling from Rab11-positive endosomes back to the plasma membrane. [3H]palmitate metabolic labeling, mutagenesis of CQC motif, membrane trafficking rate constant calculations, EGFP-Rab11 co-localization, co-immunoprecipitation with AP-1 The Journal of biological chemistry High 16507569
2009 MUC1 is a substrate for gamma-secretase: after TACE/ADAM17 ectodomain shedding, the resulting 15 kDa membrane-bound C-terminal fragment (CTF15) undergoes presenilin-dependent gamma-secretase cleavage. Mature nicastrin (the substrate receptor of gamma-secretase) co-immunoprecipitates with CTF15. Gamma-secretase inhibition causes CTF15 accumulation; subsequent degradation is non-proteasomal. Gamma-secretase inhibitors, TACE/ADAM17 inhibitors, nicastrin siRNA knockdown, co-immunoprecipitation of nicastrin with CTF15, Western blotting for cleavage products Journal of cellular biochemistry High 19711367
2013 PPARγ acts as an E3 ubiquitin ligase that binds MUC1-C and induces its proteasome-dependent ubiquitination and degradation, identifying Lys134 of MUC1-C as critical for PPARγ-mediated degradation; this terminates MUC1-C-mediated cell proliferation independently of PPARγ transcriptional activity. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (Lys134), proteasome inhibitor treatment, cell proliferation assay Oncogene High 24292674
2016 MUC1-C drives MYC expression in multiple myeloma by occupying the MYC promoter via a β-catenin/TCF4-mediated mechanism; MUC1-C increases β-catenin occupancy on the MYC promoter and forms a complex with β-catenin and TCF4. CRISPR/Cas9 MUC1-C silencing, ChIP, co-immunoprecipitation, qRT-PCR, GO-203 inhibitor treatment Blood High 26907633
2016 MUC1-C drives BMI1 transcription by a MYC-dependent mechanism and blocks miR-200c-mediated BMI1 downregulation. MUC1-C directly binds BMI1 and promotes BMI1 occupancy on the CDKN2A (p16INK4a) promoter, linking MUC1-C to PRC1-mediated epigenetic silencing of p16INK4a. Co-immunoprecipitation, ChIP, miRNA reporter assay, gene silencing, inhibitor (GO-203) treatment Oncogene High 27893710
2016 MUC1-C associates with ZEB1 on the CRB3 promoter to repress CRB3 transcription. Loss of CRB3 suppresses the Hippo pathway (reduced LATS1/2 phosphorylation), activating YAP. MUC1-C then interacts with YAP, promotes YAP/β-catenin complex formation, and induces WNT target MYC expression. ChIP, co-immunoprecipitation, siRNA knockdown, promoter reporter assay, phosphorylation analysis Molecular cancer research High 27658423
2007 MUC1 cytoplasmic tail sequesters β-catenin away from E-cadherin, reduces β-catenin nuclear translocation, decreases LEF-1 activation, and suppresses cyclin D1 and c-Myc expression, resulting in inhibition of cell proliferation. Transfection of MUC1 cytoplasmic tail (CD8/MUC1 fusion), co-immunoprecipitation, luciferase reporter (LEF-1), Western blotting for cyclin D1/c-Myc, proliferation assay with Muc1+/+ vs. Muc1−/− primary cells Biochimica et biophysica acta High 17524503
2004 MUC1 (CD227) cytoplasmic domain is tyrosine-phosphorylated upon T cell receptor (TCR) ligation and associates with the Src-family kinase p56lck in Jurkat T cells and normal human T cells. MUC1 knockdown by siRNA reduces TCR-mediated Ca2+ influx, ERK1/2 phosphorylation, CD69 expression, proliferation, and IL-2 production. Co-immunoprecipitation of MUC1 with p56lck, low-density membrane fractionation, siRNA knockdown, flow cytometry, Ca2+ flux measurement Journal of leukocyte biology High 15513966
2001 Muc1 mucins expressed on the cell surface serve as adhesion sites for Pseudomonas aeruginosa; deletion of the extracellular domain by mutation or proteolytic cleavage with neutrophil elastase abolishes bacterial adhesion to Muc1-expressing CHO cells. Stable transfection of hamster Muc1 cDNA into CHO cells, bacterial adhesion assay, neutrophil elastase cleavage, extracellular domain deletion mutant American journal of physiology. Lung cellular and molecular physiology High 11133508
2007 Neutrophil elastase stimulates MUC1 transcription in lung epithelial cells via a PKCδ→Duox1→ROS→TACE→TNF-α→TNFR1→ERK1/2→Sp1 signaling pathway, distinct from the MUC5AC pathway which shares components only up to TACE. Pharmacological inhibitors, dominant-negative mutants, RNA interference, soluble receptor blocking, transcription reporter assay American journal of respiratory cell and molecular biology High 17600314
2019 TGF-β1 phosphorylates SMAD3, which increases phosphorylation of MUC1-CT at Thr41 and Tyr46, activating β-catenin to form phospho-SMAD3/MUC1-CT and MUC1-CT/β-catenin nuclear complexes that promote myofibroblast transition, cell senescence, and fibroblast proliferation. Galectin-3 directly activates MUC1-CT and serves as a bridge between the TGF-β receptor and MUC1-C, providing TGF-β1-independent activation. Inhibition of MUC1-CT nuclear translocation (GO-201 or siRNA) or Muc1 knockout reduces bleomycin-induced lung fibrosis. Phosphorylation analysis (Thr41/Tyr46), co-immunoprecipitation, nuclear fractionation, siRNA, GO-201 inhibitor, MUC1-knockout mice + bleomycin model, in vitro myofibroblast transition assays Thorax High 31801904
2015 In ischemia-reperfusion injury, Muc1 translocates from the apical surface to the cytoplasm and nucleus of renal tubular epithelia. Muc1 knockout mice show worse kidney damage, reduced HIF-1α levels, reduced induction of HIF-1 target glycolytic genes, and prolonged AMPK activation, indicating that Muc1 enhances the HIF-1α protective pathway during ischemic stress. Immunofluorescence localization (apical→cytoplasmic/nuclear shift), Muc1 knockout mice + IRI model, HIF-1α protein measurement, qPCR for HIF-1 target genes, AMPK activation assay American journal of physiology. Renal physiology High 25925251
2020 MUC1-C upregulates CDA (cytidine deaminase) expression by occupying the CDA promoter upon ER stress induction, increasing CDA activity and driving deoxycytidine-to-deoxyuridine metabolic reprogramming. The resulting deoxyuridine mitigates ER stress-induced cytotoxicity and ROS, providing cancer cell survival advantage. ChIP showing MUC1-C occupancy on CDA promoter, CDA activity assay, transcriptomic analysis, metabolomic analysis, MUC1 knockdown, CDA/pathway inhibitors Oncogene High 32103170
2016 MUC1 stimulates EGFR gene expression in endometrial cancer: MUC1 directly binds to two regions of the EGFR promoter (−627/−511 and −172/−64), and MUC1 knockout (CRISPR/Cas9) or siRNA knockdown reduces EGFR mRNA, protein, and downstream signaling. siRNA knockdown, CRISPR/Cas9 knockout, ChIP showing MUC1 binding to EGFR promoter, Western blotting, qPCR, proliferation assay Oncotarget High 27092881
2020 MUC1-C suppresses androgen receptor (AR) axis signaling and induces BRN2 via a MYC→BRN2 pathway; it also induces MYCN, EZH2, and neuroendocrine markers (ASCL1, AURKA, SYP), suppresses p53, and induces Yamanaka pluripotency factors (OCT4, SOX2, KLF4, MYC), driving cancer stem cell self-renewal and lineage plasticity toward neuroendocrine prostate cancer. siRNA knockdown, CRISPR editing, inhibitor treatment, ChIP for promoter occupancy, gene expression analysis, self-renewal (sphere formation) and tumorigenicity assays Nature communications High 31953400
2009 MUC1-C binds directly to β-catenin and EGFR through tandem sequences in its cytoplasmic domain; a MUC1 inhibitory peptide (PMIP) blocks both MUC1/β-catenin and MUC1/EGFR interactions in a dominant-negative fashion, induces ligand-dependent EGFR degradation, and reduces breast cancer cell proliferation, migration, invasion, and tumor growth in vivo. Peptide competition assay, co-immunoprecipitation, receptor degradation assay, in vitro proliferation/migration/invasion assays, SCID mouse xenograft model, MMTV-pyVmT transgenic mouse model Clinical cancer research High 19118037
1999 Muc1 null mice develop bacterial conjunctivitis (coagulase-negative Staphylococcus, Streptococcus type alpha, Corynebacterium group G2) at significantly higher rates than wild-type mice, establishing that Muc1 plays a critical protective role at the ocular epithelial surface against bacterial infection. Muc1 knockout mouse model, bacterial speciation of infected tissue, immunofluorescence for Muc1 protein in conjunctiva/Harderian gland, Northern blot/RT-PCR for transcript Investigative ophthalmology & visual science High 10359313
2016 MUC1/Muc1 is predominantly expressed in classically activated (M1) macrophages; MUC1/Muc1-deficiency increases macrophage adhesion and phagocytosis of P. aeruginosa and E. coli, and augments ROS production and TNF-α release, demonstrating that MUC1 counter-regulates macrophage phagocytic activity in an anti-inflammatory manner. M1 polarization and Pa stimulation increase MUC1 ectodomain shedding via TACE. Muc1 knockout macrophages (M0/M1/M2 polarization), phagocytosis assays, ROS measurement, ELISA for TNF-α, TACE inhibitor, flow cytometry American journal of respiratory cell and molecular biology High 26393683
1996 A secreted MUC1 isoform (MUC1/SEC), produced by alternative splicing incorporating intron 2 sequence and lacking a transmembrane domain, is expressed at the protein level by breast cancer cells and is detectable in sera of breast cancer patients. Generation of isoform-specific monoclonal antibodies against the unique sec peptide, Western blotting of secreted proteins, immunoreactivity with recombinant MUC1/SEC, inhibition by sec peptide Biochemical and biophysical research communications Medium 8912645
2002 MUC1 cytoplasmic domain is tyrosine-phosphorylated in activated human T cells and dendritic cells (DC), and associates with other phosphoproteins, indicating a role in signal transduction in these hematopoietic cells. Flow cytometry for CD227 expression, phosphotyrosine Western blotting of CD227 immunoprecipitates from activated T cells and DC, in vitro DC culture activation Journal of leukocyte biology Medium 12377938
2017 MUC1 induces acquired chemoresistance by upregulating ABCB1 (P-glycoprotein) through EGFR activation and nuclear translocation; targeted suppression of EGFR or ABCB1 reverses MUC1-mediated drug resistance in vitro and in xenograft models. Gain- and loss-of-function MUC1 models, shRNA and inhibitors targeting EGFR and ABCB1, xenograft mouse model, Western blotting for EGFR nuclear translocation Cell death & disease Medium 28796259
2017 MUC1 expression enhances glycolysis, pentose phosphate pathway flux, and nucleotide biosynthesis in pancreatic cancer cells, conferring radiation resistance by maintaining high nucleotide pools and reducing DNA damage; glycolysis inhibition with 3-bromopyruvate abrogates MUC1-mediated radiation resistance both in vitro and in vivo. MUC1 knockdown and overexpression models, metabolomic analysis, clonogenicity and cytotoxicity assays, DNA damage (γH2AX) measurement, 3-bromopyruvate rescue in vitro and in vivo xenograft Clinical cancer research Medium 28720669
1998 Muc1 expression in rabbit uterine epithelium is upregulated ~10-fold by progesterone and dramatically reduced locally at implantation sites; blastocyst-derived signals (demonstrated by coculture of uterine epithelial cells with trophoblastic vesicles) locally remove Muc1 from the apical epithelial surface, facilitating embryo attachment. Northern blot for Muc1 mRNA at defined pregnancy stages, immunofluorescence localization, short-term coculture of uterine epithelial cells with trophoblastic vesicles Endocrinology Medium 9421424
2022 YBX1 transcription factor directly binds the MUC1 promoter at position −1480/−1476 and activates MUC1 transcription, contributing to lung adenocarcinoma stemness and metastasis downstream of YBX1. ChIP assay, dual-luciferase reporter assay, YBX1 silencing/overexpression with MUC1 rescue, xenograft and metastasis mouse models Frontiers in oncology Medium 34976785
2022 MUC1-C enhances stability of EGFRvIII in glioblastoma by preventing its lysosomal degradation; MUC1-C knockdown increases EGFRvIII-lysosome colocalization. MUC1-C upregulation in EGFRvIII-positive cells occurs via NF-κB, forming a positive feedback loop between EGFRvIII and MUC1. CRISPR-Cas9 library screening, siRNA knockdown, immunofluorescence colocalization with lysosome markers, NF-κB pathway inhibitor, Western blotting Pharmacological research Medium 36516884
2012 MUC1 and c-Met interact physically in hepatocellular carcinoma (HCC) cells; HGF-induced c-Met phosphorylation decreases this interaction and downregulates MUC1 expression. Conversely, MUC1 siRNA silencing increases HGF-induced c-Met activation and cell motility/invasion via the β-catenin/c-Myc pathway. Co-immunoprecipitation of MUC1 and c-Met, siRNA silencing, c-Met inhibitor, migration/invasion assays, β-catenin/c-Myc Western blotting Molecular cancer Medium 22962849

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 MUC1, the renaissance molecule. Journal of mammary gland biology and neoplasia 475 11547902
1999 MUC1 and cancer. Biochimica et biophysica acta 386 10571020
2004 MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reproductive biology and endocrinology : RB&E 224 14711375
2021 MUC1: Structure, Function, and Clinic Application in Epithelial Cancers. International journal of molecular sciences 209 34207342
1998 Tolerance and immunity to MUC1 in a human MUC1 transgenic murine model. Cancer research 178 9443411
2003 Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics. Human molecular genetics 172 14570709
2007 The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Molecular cell 160 17889671
2006 MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. Molecular cell 158 16427018
2013 MUC1 and metastatic cancer: expression, function and therapeutic targeting. Cell adhesion & migration 153 23303343
2007 MUC1: a target molecule for cancer therapy. Cancer biology & therapy 134 18027437
2020 MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer. Nature communications 127 31953400
2002 MUC1 and the immunobiology of cancer. Journal of mammary gland biology and neoplasia 126 12463741
1998 Progesterone and implanting blastocysts regulate Muc1 expression in rabbit uterine epithelium. Endocrinology 126 9421424
1996 Significance of MUC1 and MUC2 mucin expression in colorectal cancer. Journal of clinical pathology 111 8813954
2015 MUC1 (CD227): a multi-tasked molecule. Cellular and molecular life sciences : CMLS 109 26294353
2001 Muc1 mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa. American journal of physiology. Lung cellular and molecular physiology 108 11133508
2004 MUC1 and MUC2 in pancreatic neoplasia. Journal of clinical pathology 106 15113850
1997 Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours. The Journal of pathology 103 9422987
2006 Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome. Kidney international 98 16883323
2011 MUC1-C oncoprotein promotes STAT3 activation in an autoinductive regulatory loop. Science signaling 92 21325207
2015 MUC1-C activates the TAK1 inflammatory pathway in colon cancer. Oncogene 90 25659581
2000 MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines. Cancer immunology, immunotherapy : CII 90 10630311
1994 Developmental expression of mucin genes MUC1 and MUC2. Journal of cell science 89 7515892
2006 Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas. The Prostate 85 16302265
2000 Human MUC1 mucin: a multifaceted glycoprotein. The International journal of biological markers 85 11192832
2017 MUC1-Mediated Metabolic Alterations Regulate Response to Radiotherapy in Pancreatic Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 83 28720669
2014 MUC1: a novel metabolic master regulator. Biochimica et biophysica acta 83 24418575
2012 MUC1 immunotherapy is here to stay. Expert opinion on biological therapy 83 22998452
2017 MUC1 induces acquired chemoresistance by upregulating ABCB1 in EGFR-dependent manner. Cell death & disease 82 28796259
1999 Bacterial conjunctivitis in Muc1 null mice. Investigative ophthalmology & visual science 82 10359313
2008 Phosphorylation of MUC1 by Met modulates interaction with p53 and MMP1 expression. The Journal of biological chemistry 79 18625714
1998 MUC1 and endometrial receptivity. Molecular human reproduction 79 9872358
1997 Posterior end mark 2 (pem-2), pem-4, pem-5, and pem-6: maternal genes with localized mRNA in the ascidian embryo. Developmental biology 72 9441682
1995 Is episialin/MUC1 involved in breast cancer progression? Cancer letters 72 7720039
2017 MUC1 Aptamer Targeted SERS Nanoprobes. Advanced functional materials 69 29147108
2016 MUC1-C drives MYC in multiple myeloma. Blood 68 26907633
2002 MUC1 epithelial mucin (CD227) is expressed by activated dendritic cells. Journal of leukocyte biology 67 12377938
1998 Normal reproductive and macrophage function in Pem homeobox gene-deficient mice. Developmental biology 67 9769172
2012 Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis. Molecular cancer 66 22962849
2008 MUC1 mucin: a peacemaker in the lung. American journal of respiratory cell and molecular biology 62 18617677
2024 The Role of MUC1 in Renal Cell Carcinoma. Biomolecules 61 38540735
2010 MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. The Journal of clinical endocrinology and metabolism 61 20826587
2009 Intracellular MUC1 peptides inhibit cancer progression. Clinical cancer research : an official journal of the American Association for Cancer Research 61 19118037
2003 Mutations of the Uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domains. Kidney international 61 14531790
2017 MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function. Journal of clinical medicine 59 29186029
2016 Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines. Vaccines 59 27472370
1996 Detection of a secreted MUC1/SEC protein by MUC1 isoform specific monoclonal antibodies. Biochemical and biophysical research communications 57 8912645
2022 Expression of MUC1 in different tumours and its clinical significance (Review). Molecular and clinical oncology 56 36479256
2020 MUC1-C drives stemness in progression of colitis to colorectal cancer. JCI insight 56 32427590
2006 Recycling of MUC1 is dependent on its palmitoylation. The Journal of biological chemistry 55 16507569
1991 Production of MUC1 and MUC2 mucins by human tumor cell lines. Biochemical and biophysical research communications 54 1713449
2016 MUC1-C activates BMI1 in human cancer cells. Oncogene 52 27893710
1999 Diverse glycosylation of MUC1 and MUC2: potential significance in tumor immunity. Journal of biochemistry 52 10578046
2005 Expression of MUC1 and its significance in hepatocellular and cholangiocarcinoma tissue. World journal of gastroenterology 51 16094706
1997 MUC1 and MUC2 mucins in flat and polypoid colorectal adenomas. Journal of clinical pathology 51 9215126
2015 MUC1 as a potential target in anticancer therapies. American journal of clinical oncology 50 23608828
2004 MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells. Journal of leukocyte biology 49 15513966
2013 PPARγ E3 ubiquitin ligase regulates MUC1-C oncoprotein stability. Oncogene 48 24292674
2001 MUC1 gene polymorphism in the gastric carcinogenesis pathway. European journal of human genetics : EJHG 47 11464247
2002 Androgen-dependent regulation of human MUC1 mucin expression. Neoplasia (New York, N.Y.) 46 11922395
2024 MUC1 and MUC16: critical for immune modulation in cancer therapeutics. Frontiers in immunology 45 38361923
2007 The signaling pathway involved in neutrophil elastase stimulated MUC1 transcription. American journal of respiratory cell and molecular biology 43 17600314
1998 Androgen regulation of the Pem homeodomain gene in mice and rat Sertoli and epididymal cells. Journal of andrology 43 9537288
2021 Crosstalk between MUC1 and VEGF in angiogenesis and metastasis: a review highlighting roles of the MUC1 with an emphasis on metastatic and angiogenic signaling. Cancer cell international 42 33836774
2021 MUC1 is an oncoprotein with a significant role in apoptosis (Review). International journal of oncology 41 34278474
2022 PEM-seq comprehensively quantifies DNA repair outcomes during gene-editing and DSB repair. STAR protocols 38 35462794
2016 MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway. Molecular cancer research : MCR 38 27658423
2015 MUC1-mediated motility in breast cancer: a review highlighting the role of the MUC1/ICAM-1/Src signaling triad. Clinical & experimental metastasis 38 25759211
2015 Muc1 is protective during kidney ischemia-reperfusion injury. American journal of physiology. Renal physiology 38 25925251
2008 Overexpression and altered glycosylation of MUC1 in malignant mesothelioma. British journal of cancer 38 18454162
2017 MUC1 facilitates metabolomic reprogramming in triple-negative breast cancer. PloS one 37 28464016
2004 Homozygosity for uromodulin disorders: FJHN and MCKD-type 2. Kidney international 37 15253706
1992 Expression of MUC1 and MUC2 mucins by human tumor cell lines. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 1283926
2020 MUC1 oncoprotein mitigates ER stress via CDA-mediated reprogramming of pyrimidine metabolism. Oncogene 36 32103170
2009 MUC1 is a substrate for gamma-secretase. Journal of cellular biochemistry 36 19711367
2011 MUC1 and MUC4: switching the emphasis from large to small. Cancer biotherapy & radiopharmaceuticals 35 21728842
2022 MUC1: An emerging target in cancer treatment and diagnosis. Bulletin du cancer 34 36184332
2019 Microbe-MUC1 Crosstalk in Cancer-Associated Infections. Trends in molecular medicine 33 31753595
2008 MUC1 and colorectal cancer pathophysiology considerations. World journal of gastroenterology 33 18407586
2019 MUC1 intracellular bioactivation mediates lung fibrosis. Thorax 32 31801904
2008 Strategies used for MUC1 immunotherapy: preclinical studies. Expert review of vaccines 32 18767945
2000 MUC1 in carcinoma-host interactions. Glycoconjugate journal 32 11421355
2016 MUC1 stimulates EGFR expression and function in endometrial cancer. Oncotarget 31 27092881
2009 Expression of human MUC1 during early pregnancy in the human MUC1 transgenic mouse model. Biology of reproduction 31 19684334
2007 MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. Biochimica et biophysica acta 31 17524503
2009 Cortical anchorages and cell type segregations of maternal postplasmic/PEM RNAs in ascidians. Developmental biology 30 19735652
2000 Immunotherapy with mannan-MUC1 and IL-12 in MUC1 transgenic mice. Vaccine 30 10930667
1993 Characterization and overexpression of the pem gene encoding pectin methylesterase of Erwinia chrysanthemi strain 3937. Gene 30 8370537
2022 Emergence of MUC1 in Mammals for Adaptation of Barrier Epithelia. Cancers 29 36230728
2020 Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer. Medical oncology (Northwood, London, England) 29 32219571
2018 Role of transmembrane glycoprotein mucin 1 (MUC1) in various types of colorectal cancer and therapies: Current research status and updates. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 30257347
2022 MUC1 promotes glioblastoma progression and TMZ resistance by stabilizing EGFRvIII. Pharmacological research 28 36516884
2016 MUC1 in hematological malignancies. Leukemia & lymphoma 28 27347699
1999 Epithelial mucin-1 (MUC1) expression and MA5 anti-MUC1 monoclonal antibody targeting in multiple myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research 28 10541345
1992 Protein energy malnutrition (PEM), brain and various facets of child development. Indian journal of pediatrics 28 1383143
2021 YBX1 Enhances Metastasis and Stemness by Transcriptionally Regulating MUC1 in Lung Adenocarcinoma. Frontiers in oncology 27 34976785
2016 Membrane-Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages. American journal of respiratory cell and molecular biology 27 26393683
2014 Mucin 1 gene (MUC1) and gastric-cancer susceptibility. International journal of molecular sciences 27 24810688
2004 Tumor-specific immunity in MUC1.Tg mice induced by immunization with peptide vaccines from the cytoplasmic tail of CD227 (MUC1). Cancer immunology, immunotherapy : CII 27 15696607
2002 Constitutive and inducible expression of the epithelial antigen MUC1 (CD227) in human T cells. Experimental cell research 26 12372344

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