Affinage

CLDN1

Claudin-1 · UniProt O95832

Length
211 aa
Mass
22.7 kDa
Annotated
2026-04-28
57 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLDN1 is a four-transmembrane tight junction protein that establishes paracellular barrier function in epithelia and whose subcellular localization, transcriptional regulation, and protein interactions determine context-dependent roles in tissue homeostasis, differentiation, and cancer. CLDN1 alone is sufficient to reconstitute paracellular flux inhibition at tight junctions independently of occludin, and its first extracellular loop mediates this barrier activity; CRISPR knockout in keratinocytes abolishes barrier function, impairs stratification, and reduces differentiation markers including filaggrin (PMID:11920682, PMID:38711223, PMID:31381894). CLDN1 transcription is suppressed by STAT3 (downstream of IL-33/ERK), BHLHE40–SP1 interaction, and EZH2-mediated H3K27me3 at its promoter, and positively regulated by a WAKMAR2–c-Fos complex; post-transcriptionally, CLDN1 mRNA is directly targeted by miR-155, miR-29a, miR-142-5p, and miR-31-3p, and stabilized by LIN28B binding (PMID:29534857, PMID:29704436, PMID:34789399, PMID:36461623, PMID:37318881). In cancer, CLDN1 exerts context-dependent effects: it promotes EMT through SNAI1 interaction and Notch signaling, drives autophagy and drug resistance via AMPK/STAT1/ULK1, and acts as a metastasis suppressor in lung adenocarcinoma through the CLDN1–EPHB6–ERK1/2–SLUG feedback axis, with membrane versus nuclear localization determining oncogenic or tumor-suppressive outcomes (PMID:27974683, PMID:31498437, PMID:32754286, PMID:28614291). Biallelic loss-of-function mutations in CLDN1, including the p.Arg81His variant that causes protein mislocalization and disrupted tight junction ultrastructure, cause autosomal recessive ichthyosis-associated syndromes (ILVASC/neonatal ichthyosis-sclerosing cholangitis) (PMID:35920354, PMID:37814412).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 Medium

    Identification of CLDN1 as a tight junction transmembrane protein established it as a structural component of the epithelial paracellular barrier, opening the question of whether it had autonomous barrier-forming activity.

    Evidence cDNA cloning, sequence analysis, and tissue expression profiling of the human gene initially named SEMP1

    PMID:9931503

    Open questions at the time
    • No functional data demonstrating barrier activity
    • Relationship to other claudin family members at TJs unknown
  2. 2002 High

    Reconstitution experiments showed CLDN1 alone is sufficient for paracellular gate function independently of occludin, establishing its autonomous role in barrier formation.

    Evidence Retroviral re-expression in CLDN1-negative breast tumor cells with paracellular flux assays and immunofluorescence

    PMID:11920682

    Open questions at the time
    • Which extracellular domain mediates barrier activity not yet mapped
    • Mechanism of CLDN1 homotypic or heterotypic interactions unknown
  3. 2004 Medium

    The finding that membrane-localized CLDN1 induces apoptosis in 3D tumor spheroids while cytosolic CLDN1 does not revealed that subcellular localization determines CLDN1's functional output, introducing the concept of context-dependent pro- versus anti-tumorigenic roles.

    Evidence 3D spheroid culture of breast cancer cells with retroviral CLDN1 transduction, apoptosis assays, and immunofluorescence

    PMID:14648703

    Open questions at the time
    • Mechanism of CLDN1 mislocalization to cytosol unresolved
    • Whether nuclear localization (later observed) has distinct functions not yet addressed
  4. 2013 Medium

    Identification of miR-155 and phospho-ΔNp63α/miR-185-5p as direct post-transcriptional regulators of CLDN1 via its 3′-UTR established that CLDN1 expression is tightly controlled at the mRNA level, explaining how barrier function and invasion can be dynamically tuned.

    Evidence Luciferase 3′-UTR reporter assays, miRNA transfection, and promoter reporter assays in ovarian cancer and epithelial cells

    PMID:23523916 PMID:24070899

    Open questions at the time
    • Full repertoire of miRNAs targeting CLDN1 not defined
    • Relative contribution of transcriptional vs. post-transcriptional regulation in specific tissues unknown
  5. 2016 Medium

    Demonstration that CLDN1 interacts with SNAI1 to drive EMT and that Nm23H1/AKT signaling regulates CLDN1 expression linked CLDN1 to invasion/metastasis signaling networks beyond its structural barrier role.

    Evidence Co-immunoprecipitation of CLDN1–SNAI1 with functional EMT readouts in cervical cancer cells; AKT inhibitor rescue of CLDN1 in esophageal cancer cells

    PMID:27376780 PMID:27974683

    Open questions at the time
    • CLDN1–SNAI1 interaction domain not mapped
    • Whether CLDN1 directly activates SNAI1 transcriptional activity or sequesters it is unknown
    • Reciprocal Co-IP for CLDN1–SNAI1 not reported
  6. 2017 Medium

    Multiple studies converged on CLDN1's signaling capacity: it activates Notch (NICD/Hes-1) in bronchial epithelium and promotes autophagy via ULK1 phosphorylation in NSCLC, revealing CLDN1 as a signal transducer beyond its structural role.

    Evidence siRNA knockdown with Notch activator rescue in bronchial cells; ULK1 phosphorylation and autophagosome analysis in NSCLC lines

    PMID:28316062 PMID:28614291

    Open questions at the time
    • How CLDN1 activates Notch cleavage mechanistically is unknown
    • Whether autophagy activation requires membrane or nuclear CLDN1 not tested
  7. 2018 High

    Identification of STAT3 direct binding to the CLDN1 promoter (via IL-33/ERK) and BHLHE40–SP1 interaction blocking SP1-dependent transcription defined two distinct transcriptional repression mechanisms, explaining how inflammatory and developmental cues silence CLDN1.

    Evidence EMSA showing STAT3 binding to CLDN1 promoter in keratinocytes; Co-IP plus deletion mutant analysis of BHLHE40–SP1 with CLDN1 promoter reporters

    PMID:29534857 PMID:29704436

    Open questions at the time
    • Whether STAT3 and BHLHE40/SP1 act on the same or distinct CLDN1 promoter elements not resolved
    • Combinatorial transcriptional regulation in vivo not tested
  8. 2019 High

    The CLDN1–EPHB6–ERK1/2–SLUG feedback axis was delineated as a metastasis-suppressive circuit in lung adenocarcinoma disrupted by promoter hypermethylation, establishing CLDN1 as a bona fide metastasis suppressor in this context and reconciling its dual role in cancer.

    Evidence Co-IP, ChIP, methylation-specific PCR, pyrosequencing, reporter assays, and xenograft experiments in lung adenocarcinoma models

    PMID:32754286

    Open questions at the time
    • Whether this feedback loop operates in other carcinoma types unknown
    • Direct structural basis for CLDN1–EPHB6 interaction not determined
  9. 2019 Medium

    Functional demonstration that first extracellular loop peptides transiently open tight junctions mapped the barrier-mediating domain and enabled translational application for transepithelial drug/antigen delivery.

    Evidence Peptide design from ECL1, TEER and FITC-dextran assays in lung epithelial cells and primary keratinocytes, mouse epicutaneous immunization

    PMID:31381894

    Open questions at the time
    • Whether peptides disrupt CLDN1 homotypic or heterotypic claudin interactions not distinguished
    • Long-term safety of barrier disruption not assessed
  10. 2021 High

    EZH2-mediated H3K27me3 at the CLDN1 TSS was shown to epigenetically silence CLDN1 in esophageal epithelium, and LIN28B was found to directly bind and stabilize CLDN1 mRNA to activate NOTCH3-dependent metastasis, adding epigenetic and RNA-binding protein layers to CLDN1 regulation.

    Evidence ChIP-qPCR for H3K27me3 at CLDN1 TSS with EZH2 inhibitor rescue in rat model; RNA immunoprecipitation of LIN28B–CLDN1 mRNA with in vivo CRC metastasis model

    PMID:34789399 PMID:37318881

    Open questions at the time
    • Whether EZH2 and DNA methylation cooperate to silence CLDN1 not tested
    • How LIN28B binding stabilizes CLDN1 mRNA (e.g., polyA tail protection) mechanistically unclear
  11. 2022 High

    The lncRNA WAKMAR2–c-Fos complex was shown to bind the CLDN1 promoter and activate transcription, identifying a non-coding RNA–transcription factor mechanism that maintains barrier function in keratinocytes.

    Evidence RNA pulldown, ChIRP-seq mapping WAKMAR2 to CLDN1 promoter, AP-1 inhibitor reversal, in vivo UV mouse model

    PMID:36461623

    Open questions at the time
    • Whether other AP-1 family members substitute for c-Fos at the CLDN1 promoter unknown
    • Relative importance of WAKMAR2 vs. direct c-Fos binding not quantified
  12. 2022 Medium

    The CLDN1 p.Arg81His variant was shown to cause protein mislocalization and reduced expression, directly linking CLDN1 loss of function to autosomal recessive congenital ichthyosis (ILVASC), with ultrastructural TEM confirmation of disrupted tight junction architecture in patient skin.

    Evidence WES/Sanger sequencing, Western blot and immunofluorescence in transfected HaCaT cells, TEM of patient skin biopsies

    PMID:35920354 PMID:37814412

    Open questions at the time
    • Only one causative variant functionally characterized; allelic spectrum of CLDN1-associated disease not fully defined
    • Mechanism by which Arg81His disrupts folding/trafficking not resolved at atomic level
  13. 2023 High

    CRISPR knockout of CLDN1 in keratinocytes definitively demonstrated its requirement for epidermal stratification, stratum granulosum formation, and differentiation marker expression, establishing CLDN1 as essential for keratinocyte terminal differentiation beyond barrier function.

    Evidence CRISPR/Cas9 knockout in keratinocytes with monolayer barrier assays and 3D organotypic culture histology

    PMID:38711223

    Open questions at the time
    • Whether CLDN1 signals to promote differentiation or acts indirectly via barrier-dependent paracrine cues unresolved
    • Compensatory roles of other claudins in CLDN1-null epidermis not assessed
  14. 2023 Medium

    CLDN1 was found to directly interact with MMP14 and to regulate trophoblast invasion through VIM/SNAIL/IL1B/PECAM1, expanding its non-barrier functions to extracellular matrix remodeling and placental biology.

    Evidence Co-immunoprecipitation of CLDN1–MMP14 in airway smooth muscle cells; knockdown/overexpression in HTR8/SVneo trophoblast cells with invasion and tube formation assays

    PMID:37523840 PMID:37964516

    Open questions at the time
    • CLDN1–MMP14 interaction domain not mapped
    • Whether CLDN1 directly modulates MMP14 enzymatic activity or only its expression not distinguished
    • Reciprocal validation of CLDN1–MMP14 interaction needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: what determines CLDN1 membrane vs. nuclear routing and how nuclear CLDN1 mechanistically activates signaling cascades (AMPK/STAT1, Notch); whether CLDN1 functions as a signaling receptor or scaffold; and the structural basis for its diverse protein interactions (SNAI1, EPHB6, MMP14).
  • No structural model of CLDN1 in complex with any binding partner
  • Nuclear import mechanism and nuclear CLDN1 interactome undefined
  • Relative contributions of barrier vs. signaling functions in vivo not genetically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098772 molecular function regulator activity 4 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1500931 Cell-Cell communication 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 2
Partners
BHLHE40EPHB6LIN28BMMP14SNAI1SP1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CLDN1 (initially named SEMP1) encodes a tight junction-associated transmembrane protein with high identity to mouse claudin-1, functioning as a component of epithelial tight junctions involved in maintenance of cell polarity and paracellular permeability regulation. cDNA cloning, differential display, amino acid sequence analysis, tissue expression profiling Gene Medium 9931503
2002 CLDN1 protein localizes to cell-cell contact sites (tight junctions) in breast epithelial cells and, when re-expressed in CLDN1-negative breast tumor cells, reconstitutes paracellular flux inhibition independently of occludin, indicating CLDN1 alone is sufficient for gate function of tight junctions. Retroviral transduction, immunofluorescence, quantitative RT-PCR, Western blot, paracellular flux assay with fluorescent dextran Journal of cellular physiology High 11920682
2004 CLDN1 membrane localization in breast tumor spheroids induces apoptosis; cytosolic versus membrane distribution determines apoptotic outcome, and membrane-localized CLDN1 inhibits paracellular flux, suggesting CLDN1 restricts nutrient/growth factor supply in 3D tumor cultures. Retroviral transduction, FACS sorting, 3D spheroid culture, cellular immunofluorescence, apoptosis assays, paracellular flux measurement International journal of cancer Medium 14648703
2013 miR-155 directly targets the 3' UTR of CLDN1 mRNA, suppressing CLDN1 protein expression and reducing invasion and proliferation of ovarian cancer-initiating cells. Luciferase reporter assay, Western blot, RT-PCR, Transwell migration assay, xenograft tumor model FEBS letters Medium 23523916
2013 Phospho-ΔNp63α (ATM-phosphorylated) regulates CLDN1 expression through dual mechanisms: direct binding to the CLDN1 promoter to control transcription, and upregulation of miR-185-5p/downregulation of let7-5p which post-transcriptionally modulate CLDN1 via its 3'-UTR. Promoter reporter assay, miRNA transfection, 3'-UTR reporter assay, chromatin binding analysis FEBS letters Medium 24070899
2016 CLDN1 induces EMT in cervical cancer cells by interacting with SNAI1, leading to downregulation of E-cadherin and upregulation of vimentin, promoting invasion and metastasis. Overexpression in SiHa cells, Western blot, co-immunoprecipitation (CLDN1–SNAI1 interaction), Transwell invasion, xenograft model Oncotarget Medium 27974683
2016 Nm23H1 regulates CLDN1 expression via AKT signaling in esophageal squamous cell carcinoma: Nm23H1 silencing activates AKT phosphorylation, which reduces CLDN1 expression and enhances cell invasiveness; AKT inhibitor MK2206 rescues CLDN1 expression and suppresses invasion. siRNA knockdown, overexpression, Western blot, AKT inhibitor treatment, migration/invasion assays, immunofluorescence Oncogenesis Medium 27376780
2016 miR-142-5p directly targets CLDN1 (validated by luciferase assay), and its overexpression in thyrocytes reduces claudin-1 mRNA and protein levels and increases thyrocyte monolayer permeability. Luciferase reporter assay, Western blot, RT-PCR, permeability assay Journal of translational medicine Medium 27277258
2017 CLDN1 promotes EMT and migration in human bronchial epithelial cells via the Notch signaling pathway: CLDN1 knockdown reduces Notch intracellular domain (NICD) and Hes-1 levels, and Notch activator Jagged-1 reverses the protective effects of CLDN1 silencing. siRNA knockdown, Western blot, RT-PCR, Transwell assay, Notch pathway manipulation Molecular and cellular biochemistry Medium 28316062
2017 miR-29a directly targets the 3'UTR of CLDN1 mRNA (validated by dual-luciferase assay), suppressing CLDN1 expression; CLDN1 knockdown reduces HCC cell growth and migration, and overexpression of CLDN1 reverses miR-29a-mediated suppression. Dual-luciferase reporter assay, siRNA knockdown, overexpression rescue, proliferation and migration assays, in vivo tumor model Biochemical and biophysical research communications Medium 28342862
2017 CLDN1 promotes cisplatin drug resistance in NSCLC by activating autophagy through upregulation of ULK1 phosphorylation. Western blot, CCK-8 assay, confocal microscopy for autophagosomes, Transwell assay, siRNA knockdown Medical science monitor Medium 28614291
2017 TMPRSS4 regulates CLDN1 expression via ERK1/2 signaling pathway in HCC cells, and CLDN1 promotes cancer stem cell traits including tumorsphere formation. Western blot, ERK1/2 pathway inhibition, sphere formation assay, overexpression and knockdown experiments Biochemical and biophysical research communications Low 28651932
2018 IL-33 downregulates CLDN1 expression in keratinocytes through the ERK/STAT3 pathway; STAT3 directly binds to the CLDN1 promoter to suppress its transcription, impairing epithelial barrier function. MAPK inhibitors, siRNA, Western blot, RT-PCR, TEER measurement, FITC-dextran flux assay, EMSA for STAT3 binding to CLDN1 promoter Journal of dermatological science High 29534857
2018 BHLHE40 suppresses CLDN1 transcription by interacting with SP1 (not by binding E-box motifs); BHLHE40 prevents SP1 from binding to a specific motif at -233 to -61 bp upstream of the CLDN1 transcription start site. The BHLH and Orange domains of BHLHE40 are essential for this interaction with SP1. Reporter assays, co-immunoprecipitation, co-localization, siRNA, deletion mutant analysis, ChIP-like binding analysis Molecular carcinogenesis High 29704436
2019 CLDN1 acts as a metastasis suppressor in lung adenocarcinoma through a feedback loop: CLDN1 upregulates EPHB6 and enhances its activation, suppressing ERK1/2 signaling, which in turn represses SLUG (a negative regulator of CLDN1). DNA hypermethylation of the CLDN1 promoter disrupts this loop. Immunoprecipitation, immunoblots, methylation-specific PCR, pyrosequencing, chromatin immunoprecipitation, reporter assay, migration assay, sphere assay, aldefluor assay, xenograft experiments Theranostics High 32754286
2019 Peptides derived from the first extracellular loop of CLDN1 transiently disrupt tight junctions in human lung epithelial cells and delay TJ formation in primary human keratinocytes, increasing transepithelial water loss and enabling epicutaneous antigen delivery. Peptide design, TEER measurement, FITC-Dextran permeability assay, live cell imaging, mouse epicutaneous immunization, antibody titer measurement The Journal of investigative dermatology Medium 31381894
2019 CLDN1 promotes autophagy and tumor proliferation/metastasis in esophageal squamous cell carcinoma via the AMPK/STAT1/ULK1 signaling pathway, and notably localizes predominantly to the nucleus in ESCC tumor cells. Western blot, immunohistochemistry, in vitro proliferation/migration/invasion assays, in vivo xenograft, immunofluorescence for nuclear distribution, pathway analysis Journal of cellular physiology Medium 31498437
2020 hsa-miR-31-3p directly targets the 3'UTR of CLDN1 (confirmed by dual-luciferase assay), is induced by UVB and UVA irradiation, and its overexpression increases keratinocyte permeability and reduces claudin-1 expression, impairing skin barrier function. Dual-luciferase reporter assay, Western blot, FITC-Dextran permeability assay, UV irradiation, RT-PCR Biochemical and biophysical research communications Medium 32907715
2021 EZH2-mediated H3K27me3 histone modification accumulates at the CLDN1 transcription start site to suppress CLDN1 transcription; EZH2 inhibition with GSK126 restores CLDN1 expression and barrier function in esophageal epithelium. ChIP-qPCR, Western blot, RNA sequencing, TEER measurement, FITC-dextran flux assay, EGDA rat model, EZH2 inhibitor treatment Digestive and liver disease High 34789399
2021 LIN28B directly binds to CLDN1 mRNA (via RNA immunoprecipitation) and posttranscriptionally upregulates CLDN1, which enhances collective invasion, migration, and metastatic liver tumor formation; NOTCH3 acts downstream of the LIN28B/CLDN1 axis. RNA immunoprecipitation, siRNA knockdown, overexpression, in vitro invasion/migration assays, murine CRC metastasis model, bulk RNA sequencing, pharmacological NOTCH3 inhibition JCI insight High 37318881
2022 A missense variant p.Arg81His in CLDN1 causes decreased protein expression and mislocation of CLDN1 away from the membrane (confirmed in transfected HaCaT cells), with 3D protein modeling predicting deleterious conformational changes, resulting in autosomal recessive congenital ichthyosis. Whole exome sequencing, Sanger sequencing, 3D protein modeling, Western blot, immunofluorescence confocal microscopy in transfected cells American journal of medical genetics Medium 35920354
2023 CLDN1 loss in keratinocytes (CRISPR/Cas9 KO) results in significantly reduced barrier function, decreased filaggrin and cytokeratin-10 expression, diminished stratification/stratum granulosum formation, and increased proliferative keratinocytes in the basal layer. CRISPR/Cas9 knockout, monolayer and organotypic culture barrier assays, gene expression analysis, histological analysis Experimental dermatology High 38711223
2023 CLDN1 promotes proliferation and migration of airway smooth muscle cells by directly interacting with MMP14 (co-immunoprecipitation) and positively regulating MMP14 expression; MMP14 overexpression rescues the inhibitory effects of CLDN1 silencing. Co-immunoprecipitation, Western blot, siRNA knockdown, overexpression, CCK-8 assay, EdU assay, Transwell assay, ELISA Autoimmunity Medium 37964516
2023 CLDN1 promotes trophoblast invasion and endovascular trophoblast differentiation by regulating VIM, SNAIL, IL1B, and PECAM1; knockdown suppresses invasion/migration and tube penetration while overexpression promotes these functions in HTR8/SVneo cells. siRNA knockdown, overexpression, Western blot, RT-PCR, invasion/migration assay, tube formation assay, EOPE mouse model Placenta Medium 37523840
2023 WNT7A stimulated by cancer-associated fibroblasts activates AKT signaling in oral squamous cell carcinoma cells, which downregulates CLDN1 expression, promoting cancer cell migration; AKT inhibitor MK2206 rescues CLDN1 expression and suppresses migration. Transwell coculture, microarray, knockdown, phosphokinase array, AKT inhibitor treatment, immunohistochemistry Laboratory investigation Medium 37541622
2023 Oxaliplatin-induced CLDN1 overexpression in colorectal cancer cells is mediated at least in part by activation of the MAPKp38/GSK3β/Wnt/β-catenin pathway; overexpressed CLDN1 confers resistance to apoptosis. Flow cytometry, immunofluorescence, Western blot, phosphoproteome analysis, proximity ligation assay, luciferase reporter assay, RNAseq, xenograft model Cell & bioscience Medium 37041570
2022 LncRNA WAKMAR2 directly binds c-Fos protein and recruits this complex to the CLDN1 promoter to enhance CLDN1 transcription; loss of WAKMAR2 reduces CLDN1 expression and impairs keratinocyte barrier function. RNA pulldown, promoter-reporter assay, chromatin isolation by RNA purification-sequencing (ChIRP-seq), AP-1 inhibitor treatment, in vivo mouse UV model Contact dermatitis High 36461623
2014 CLDN1 knockdown in mouse osteoblasts (MC3T3-E1) reduces cell proliferation, alkaline phosphatase activity, cyclinD1, ALP, Runx-2, osterix, and β-catenin levels, identifying CLDN1 as a positive regulator of osteoblast differentiation linked to the Wnt/β-catenin pathway. Lentiviral shRNA knockdown, proliferation assay, ALP activity assay, RT-PCR, Western blot PloS one Medium 25479235
2021 CLDN1 regulates trophoblast apoptosis via BIRC3: CLDN1 knockdown reduces BIRC3 expression and increases cleaved PARP, while BIRC3 overexpression rescues the apoptotic effect of CLDN1 knockdown. siRNA knockdown, overexpression rescue, RNA-seq, Western blot, RT-PCR, immunohistochemistry, flow cytometry Reproduction Medium 33784242
2023 In the ILVASC syndrome, the CLDN1 p.Arg81His variant causes distorted tight junction architecture (confirmed by transmission electron microscopy of patient skin), providing direct ultrastructural evidence that CLDN1 is essential for normal TJ assembly in human epidermis. Transmission electron microscopy, haplotype analysis, immunofluorescence Clinical genetics Medium 37814412

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 MicroRNA-155 is a novel suppressor of ovarian cancer-initiating cells that targets CLDN1. FEBS letters 111 23523916
2004 Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids. International journal of cancer 101 14648703
1999 SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily. Gene 76 9931503
2018 IL-33 down-regulates CLDN1 expression through the ERK/STAT3 pathway in keratinocytes. Journal of dermatological science 67 29534857
2002 Expression and targeting of the tight junction protein CLDN1 in CLDN1-negative human breast tumor cells. Journal of cellular physiology 59 11920682
2013 Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival. BMC cancer 49 24321518
2017 miR-29a suppresses growth and migration of hepatocellular carcinoma by regulating CLDN1. Biochemical and biophysical research communications 48 28342862
2017 CLDN1 Increases Drug Resistance of Non-Small Cell Lung Cancer by Activating Autophagy via Up-Regulation of ULK1 Phosphorylation. Medical science monitor : international medical journal of experimental and clinical research 43 28614291
2020 Inhibition of miRNA-29a regulates intestinal barrier function in diarrhea-predominant irritable bowel syndrome by upregulating ZO-1 and CLDN1. Experimental and therapeutic medicine 41 33093893
2019 CLDN1 induces autophagy to promote proliferation and metastasis of esophageal squamous carcinoma through AMPK/STAT1/ULK1 signaling. Journal of cellular physiology 39 31498437
2016 CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis. Oncotarget 37 27974683
2016 MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1. Journal of translational medicine 33 27277258
2020 LncRNA XIST Promotes Migration and Invasion of Papillary Thyroid Cancer Cell by Modulating MiR-101-3p/CLDN1 Axis. Biochemical genetics 32 33057875
2020 DNA methylation maintains the CLDN1-EPHB6-SLUG axis to enhance chemotherapeutic efficacy and inhibit lung cancer progression. Theranostics 26 32754286
2013 Expression of CLDN1 and CLDN10 in lung adenocarcinoma in situ and invasive lepidic predominant adenocarcinoma. Journal of cardiothoracic surgery 24 23591077
2017 CLDN-1 promoted the epithelial to migration and mesenchymal transition (EMT) in human bronchial epithelial cells via Notch pathway. Molecular and cellular biochemistry 22 28316062
2016 Nm23H1 mediates tumor invasion in esophageal squamous cell carcinoma by regulation of CLDN1 through the AKT signaling. Oncogenesis 21 27376780
2009 Genetic variation in CLDN1 and susceptibility to hepatitis C virus infection. Journal of viral hepatitis 21 19674288
2014 Characterization of the small exported Plasmodium falciparum membrane protein SEMP1. PloS one 19 25062022
2020 Upregulation of hsa-miR-31-3p induced by ultraviolet affects keratinocytes permeability barrier by targeting CLDN1. Biochemical and biophysical research communications 18 32907715
2023 LIN28B promotes cell invasion and colorectal cancer metastasis via CLDN1 and NOTCH3. JCI insight 17 37318881
2024 Use of a pH-responsive imatinib mesylate sustained-release hydrogel for the treatment of tendon adhesion by inhibiting PDGFRβ/CLDN1 pathway. Bioactive materials 16 38699245
2023 Improving the response to oxaliplatin by targeting chemotherapy-induced CLDN1 in resistant metastatic colorectal cancer cells. Cell & bioscience 16 37041570
2013 Phospho-ΔNp63α regulates AQP3, ALOX12B, CASP14 and CLDN1 expression through transcription and microRNA modulation. FEBS letters 15 24070899
2021 CLDN1 regulates trophoblast apoptosis and proliferation in preeclampsia. Reproduction (Cambridge, England) 14 33784242
2019 Peptides Derived from the Tight Junction Protein CLDN1 Disrupt the Skin Barrier and Promote Responsiveness to an Epicutaneous Vaccine. The Journal of investigative dermatology 14 31381894
2018 Interaction with SP1, but not binding to the E-box motifs, is responsible for BHLHE40/DEC1-induced transcriptional suppression of CLDN1 and cell invasion in MCF-7 cells. Molecular carcinogenesis 14 29704436
2017 TMPRSS4 promotes cancer stem cell traits by regulating CLDN1 in hepatocellular carcinoma. Biochemical and biophysical research communications 14 28651932
2014 Polymorphisms in the CLDN1 and CLDN7 genes are related to differentiation and tumor stage in colon carcinoma. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 14 24479816
2014 Differential expression of claudin family members during osteoblast and osteoclast differentiation: Cldn-1 is a novel positive regulator of osteoblastogenesis. PloS one 13 25479235
2023 Role of Stromal Fibroblast-Induced WNT7A Associated with Cancer Cell Migration Through the AKT/CLDN1 Signaling Axis in Oral Squamous Cell Carcinoma. Laboratory investigation; a journal of technical methods and pathology 10 37541622
2022 CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy. Cancers 10 36291810
2015 rs17501976 polymorphism of CLDN1 gene is associated with decreased risk of colorectal cancer in a Chinese population. International journal of clinical and experimental medicine 8 25785120
2024 CLDN1 knock out keratinocytes as a model to investigate multiple skin disorders. Experimental dermatology 7 38711223
2022 Circ_0027446 induces CLDN1 expression to promote papillary thyroid cancer cell malignancy by binding to miR-129-5p. Pathology, research and practice 7 36058014
2021 Long non-coding RNA VPS9D1-AS1 promotes growth of colon adenocarcinoma by sponging miR-1301-3p and CLDN1. Human cell 7 34519940
2015 CD81 and CLDN1 polymorphisms and hepatitis C virus infection susceptibility: a case control study. Gene 7 25934191
2013 In silico analysis and validation of the proliferative potential of CLDN1 expression in gastric cancer. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 6 24579786
2022 Autosomal recessive congenital ichthyosis caused by a pathogenic missense variant in CLDN1. American journal of medical genetics. Part A 5 35920354
2022 LncRNA-WAKMAR2 regulates expression of CLDN1 to affect skin barrier through recruiting c-Fos. Contact dermatitis 5 36461623
2023 Upregulation of SEMP1 Contributes to Improving the Biological Functions of Trophoblast via the PI3K/AKT Pathway in Preeclampsia. Molecular biotechnology 3 37277581
2020 Single nucleotide variants c.-13G → C (rs17429833) and c.108C → T (rs72466472) in the CLDN1 gene and increased risk for familial colorectal cancer. Gene 3 33186612
2019 Polymorphisms in CLDN1 are associated with age and differentiation of triple-negative breast cancer patients. Bioscience reports 3 30910845
2023 Downregulation of CLDN1 impairs trophoblast invasion and endovascular trophoblast differentiation in early-onset preeclampsia. Placenta 2 37523840
2023 CLDN1 silencing suppresses the proliferation and migration of airway smooth muscle cells by modulating MMP14. Autoimmunity 2 37964516
2021 EZH2-mediated suppression of CLDN1 leads to barrier dysfunction in PPI-refractory gastroesophageal reflux disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2 34789399
2025 circFOXK2 inhibits vascular permeability and angiogenesis in advanced lung adenocarcinoma via the miR-1275/CLDN1 axis. Biochemical and biophysical research communications 1 40850182
2024 Dual roles of BK Polyomavirus in promoting urothelial carcinoma progression via regulating CLDN1. Biomarker research 1 38245774
2023 CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews. Clinical genetics 1 37814412
2008 Population genetics and comparative genetics of CLDN1, a gene involved in hepatitis C virus entry. Human heredity 1 19077439
2026 Role of HYAL1 on hyaluronan metabolism and the regulation of epidermal tight junction component CLDN1 in HaCaT cells. Archives of biochemistry and biophysics 0 41881410
2025 Neonatal ichthyosis-sclerosing cholangitis syndrome caused by a novel CLDN1 mutation: a case report and literature review. Clinical and experimental pediatrics 0 41035246
2025 PABPC3 drives ovarian cancer metastasis and drug sensitivity by downregulating CLDN1 expression. Cell death & disease 0 41249135
2025 Genome-wide CRISPR screening identifies CLDN1 as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer. Oncology letters 0 41383979
2024 Expression of CLDN1 and EGFR in PTC. Discover oncology 0 39404969
2017 [Expression of CLDN1 and Its Nuclear Distribution in Esophageal Squamous Carcinoma]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 29260519
2005 Comparative mapping of human claudin-1 (CLDN1) in great apes. Cytogenetic and genome research 0 15545735