Affinage

NECTIN4

Nectin-4 · UniProt Q96NY8

Round 2 corrected Audit flag: rerun needed
Length
510 aa
Mass
55.5 kDa
Annotated
2026-04-29
130 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

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Mechanism profile

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Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Nectin-4 was identified as a new member of the nectin family that interacts with afadin (an F-actin-associated molecule) via its carboxyl-terminal cytoplasmic sequence, co-localizes with afadin at cadherin-based adherens junctions in MDCKII epithelial cells, and trans-interacts heterophilically with nectin-1 through V domain interactions. Nectin-4-Fc binds cells expressing nectin-1 but not nectin-2, nectin-3, or PVR/CD155; reciprocal pulldown and in vitro physical interaction assays confirmed the nectin-1/nectin-4 interaction. Nectin-4 also exhibits homophilic binding. Recombinant Fc-fusion protein binding assays, co-immunoprecipitation, in vitro pulldown, co-localization by immunofluorescence in MDCKII cells The Journal of biological chemistry High 11544254
1999 The nectin family member PRR/nectin is recruited to cadherin-based adherens junctions through direct interaction of its C-terminal cytoplasmic PDZ-binding motif with the PDZ domain of afadin, an actin filament-binding protein; nectin shows Ca2+-independent cell-cell adhesion activity. Co-immunoprecipitation, co-localization by immunofluorescence, cell aggregation assays The Journal of cell biology High 10225955
2002 The V domain of nectin-1 is the major functional region mediating trans-heterointeraction with nectin-4 (and nectin-3). Affinity measurements showed the nectin-1/nectin-4 KD is ~100 nM, weaker than nectin-1/nectin-3 (KD ~1 nM) but stronger than nectin-1 homophilic (KD ~1 µM). The minimal binding region on the nectin-1 V domain was mapped to the C-C'-C"-D β-strands using chimeric nectin-1/PVR receptors. Surface plasmon resonance / affinity measurements, competitive binding with soluble Fc-fusions, monoclonal antibody blocking, chimeric receptor domain-swap experiments The Journal of biological chemistry High 12011057
2005 Nectin-4 ectodomain shedding is mediated by the metalloprotease TACE/ADAM-17: shedding is constitutively produced, strongly enhanced by PMA, inhibited by TAPI-1 or TIMP-3, abolished in TACE-deficient fibroblasts, and modulated by TACE overexpression or siRNA silencing. The soluble form (~43 kDa) corresponds to the entire nectin-4 ectodomain. siRNA knockdown and overexpression of TACE, TACE-deficient fibroblasts, pharmacological inhibitors (TAPI-1, TIMP-3), Western blot of shed product, PMA stimulation The Journal of biological chemistry High 15784625
2011 Nectin-4 (PVRL4) serves as the epithelial cell receptor for measles virus. Its membrane-distal IgV domain supports virus attachment and entry; antibodies and siRNA against PVRL4 block measles virus infection. Measles virus infection downregulates PVRL4 surface expression. Expression vector transfection of non-susceptible cell lines, siRNA knockdown, antibody blocking, virus binding assay, flow cytometry, confocal microscopy, surface biotinylation PLoS pathogens High 21901103
2011 Nectin-4 is the epithelial receptor for measles virus exit from the host: it interacts with the viral attachment protein (hemagglutinin) with high affinity through its membrane-distal IgV domain, sustains MV entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally, and is downregulated in infected epithelial cells including macaque tracheae. Functional rescue transfection in non-permissive cells, primary airway epithelial cultures, basolateral infection assays, immunohistochemistry in macaque tissues, in vitro binding assays Nature High 22048310
2012 Crystal structure of the membrane-distal IgV domain of human nectin-4 in complex with measles virus hemagglutinin (MV-H) revealed that nectin-4 binds exclusively via its N-terminal IgV domain to the β4-β5 groove of MV-H, with the contact interface dominated by hydrophobic interactions. The nectin-4 binding site on MV-H overlaps extensively with those of the other two MV receptors (CD46 and SLAM). X-ray crystallography (co-crystal structure of nectin-4 IgV domain with MV-H) Nature structural & molecular biology High 23202587
2012 Crystal structures of the full ectodomains of all four nectins and Necl-5 revealed a conserved stereotyped dimeric interface (C-C'-C"-D β-strand region of the V domain) representing the adhesive trans interaction. Quantitative binding measurements defined homophilic affinities and heterophilic specificity across the family. Targeted cross-linking confirmed the dimer interface as the adhesive trans contact. X-ray crystallography of natively glycosylated ectodomains, surface plasmon resonance, targeted cross-linking Nature structural & molecular biology High 22902367
2013 The measles virus hemagglutinin β4-β5 hydrophobic groove governs functional interactions with nectin-4 and CD46 but not SLAM. A single substitution in this groove drastically reduced nectin-4 and CD46 binding while minimally altering SLAM binding. Soluble nectin-4 blocked vaccine MV entry via nectin-4 and CD46 but only partially reduced SLAM-mediated entry. Site-directed mutagenesis of MV-H, cell fusion assays, soluble nectin-4 competition, surface plasmon resonance binding kinetics, recombinant virus construction Journal of virology High 23760251
2013 PVRL4 promotes anchorage-independent cell proliferation by driving cell-to-cell attachment and matrix-independent integrin β4/SHP-2/c-Src signaling activation. PVRL4 was identified via a gain-of-function screen for anchorage independence; breast cancer cell transformation was shown to be dependent on PVRL4, and blocking PVRL4-mediated cell-to-cell attachment with monoclonal antibodies inhibited orthotopic tumor growth in vivo. Gain-of-function screen, co-immunoprecipitation of integrin β4/SHP-2/c-Src complex, siRNA knockdown, monoclonal antibody blocking, orthotopic xenograft mouse models eLife High 23682311
2009 Exogenous expression of Nectin-4 in mammalian cells increased lamellipodia formation and invasive ability through activation of the small GTPase Rac1; siRNA-mediated suppression of Nectin-4 inhibited cell growth in lung cancer cells. siRNA knockdown, exogenous overexpression, Rac1 activation assay, invasion assay, lamellipodia quantification Cancer research Medium 19679554
2014 Nectin-4 mutations causing EDSS1 (ectodermal dysplasia-syndactyly syndrome) perturb the Rac1 pathway: trans-interaction of nectin-1 and nectin-4 induces Rac1 activation, and mutant nectin-4 (p.Val242Met, p.Thr185Met) delays cadherin recruitment at adherens junctions and impairs nectin-1 clustering at contact sites in keratinocytes, demonstrating a role for the nectin-1/nectin-4 interaction in early adherens junction formation. Patient keratinocytes and skin biopsy, ectopic expression of mutant and WT nectin-4, cell aggregation assays, immunofluorescence for cadherin/nectin-1 clustering, Rac1 activation assay The Journal of investigative dermatology High 24577405
2010 Loss-of-function mutations in PVRL4 (encoding nectin-4) cause ectodermal dysplasia-syndactyly syndrome (EDSS). Mutant nectin-4 from patients lost the capability to bind nectin-1. In patient keratinocytes, discrete hair follicle structures showed alterations in membrane localization of nectin-afadin and cadherin-catenin complexes essential for adherens junction formation, and reorganization of the actin cytoskeleton was observed. Homozygosity mapping, candidate gene sequencing, patient keratinocyte functional assays (nectin-1 binding by pull-down), immunofluorescence of adherens junction components and actin cytoskeleton in patient tissue American journal of human genetics High 20691405
2015 Nectin-4 expression in stratified epithelia is regulated by IRF6: depletion of IRF6 reduces Pvrl4 expression in keratinocytes. In AEC syndrome (p63 mutation), reduced IRF6 expression correlates with decreased Pvrl4 expression. By contrast, Pvrl1 (nectin-1) is a direct p63 target gene (p63 binds to two conserved intronic Pvrl1 enhancer regions by ChIP), but Pvrl4 regulation is independent of p63 and linked to IRF6-mediated epidermal differentiation. Chromatin immunoprecipitation (ChIP), siRNA knockdown of p63 and IRF6, qRT-PCR, p63-null mouse skin, patient AEC keratinocytes, conditional AEC mouse model Experimental dermatology Medium 25387952
2015 Measles virus spread in human airway epithelial (HAE) cells requires the nectin-4/afadin complex: afadin knockdown limited infectious-center formation, and a nectin-4 mutant lacking the afadin-binding site in its cytoplasmic tail was less effective than WT nectin-4 at promoting MV infection. Spread occurred through intercellular membrane pores (cytoplasm flow between columnar cells on lateral surfaces) rather than visible syncytia. siRNA knockdown of afadin in primary HAE cultures, nectin-4 cytoplasmic-tail mutant expression in porcine airway epithelial primary cultures, high-resolution video microscopy, GFP cytoplasm-flow assays Journal of virology High 25926640
2017 Nectin-4 ectodomain shedding in ovarian cancer is mediated by both ADAM17 and ADAM10. LPA stimulates Nectin-4 shedding; small-molecule inhibitors and siRNA knockdown of ADAM10 and ADAM17 confirmed their roles. Ascites fluid significantly increased sN4 shedding. Shed Nectin-4 is detectable at 2–20-fold higher levels in ascites than in serum. siRNA knockdown of ADAM10 and ADAM17, small-molecule inhibitor assays, LPA stimulation, ELISA quantification of shed nectin-4 in ascites and serum from matched patient samples The Journal of biological chemistry High 28232483
2018 Matrix-detached epithelial and carcinoma cells cluster spontaneously via PVRL4 (Nectin-4), activating a PVRL4/α6β4 integrin/Src signaling axis that sustains GPX4 expression to resist ferroptosis. In the absence of α6β4, PVRL4-mediated clustering increased lipid peroxidation and triggered ferroptosis; when clustering was inhibited, single cells were more susceptible to apoptosis than ferroptosis. siRNA knockdown of PVRL4 and α6β4, antibody blocking of clustering, lipid peroxidation assays, cell viability assays, Western blot for GPX4 The Journal of biological chemistry High 29934307
2017 Nectin-4 promotes breast cancer stem cell (BCSC) self-renewal and metastasis by activating WNT/β-catenin signaling via the PI3K/Akt axis. Nectin-4 depletion inhibited EMT, invasion, and WNT/β-catenin pathway activity; overexpression of Nectin-4 in null cells induced WNT/β-catenin signaling via PI3K/Akt. siRNA knockdown and overexpression in breast cancer cell lines, in vitro sphere formation, invasion assay, in vivo xenograft, ex vivo and clinical sample analysis, Western blot for PI3K/Akt/β-catenin pathway components The international journal of biochemistry & cell biology Medium 28600142
2018 Under hypoxia, ADAM-17 expressed in metastatic breast cancer stem cells sheds the nectin-4 ecto-domain into the microenvironment, which then physically interacts with integrin-β4 on endothelial cells, promoting angiogenesis via the Src/PI3K/AKT/iNOS pathway (but not Phospho-Erk or NF-κB). Co-immunoprecipitation of shed nectin-4 ecto-domain with integrin-β4, in vitro tube formation, CAM assay, in vivo angiogenesis models, pathway inhibitors, siRNA knockdown The international journal of biochemistry & cell biology Medium 30056265
2019 Nectin-4 cis-interacts with ErbB2 (and its trastuzumab-resistant splice variants p95-ErbB2 and ErbB2ΔEx16) through the third Ig-like domain of nectin-4 and domain IV of ErbB2, enhancing ErbB2 dimerization and activation and downstream PI3K/AKT signaling for DNA synthesis. Nectin-4 also enhanced p95-ErbB2-induced JAK-STAT3 signaling. Co-immunoprecipitation, domain-mapping using truncation/deletion constructs of nectin-4 and ErbB2, Western blot for PI3K-AKT and JAK-STAT3 phosphorylation, DNA synthesis assays in T47D and SUM190-PT breast cancer cell lines Scientific reports Medium 31831814
2020 Nectin-4 is a novel ligand of the immune checkpoint receptor TIGIT. Unlike other TIGIT ligands (which also bind additional receptors), Nectin-4 interacts exclusively with TIGIT. The TIGIT-Nectin-4 interaction inhibits NK cell cytotoxicity; blocking Nectin-4 antibodies enhanced tumor cell killing in vitro and in vivo. Fusion protein staining of NK cells, TIGIT binding assays, NK cytotoxicity killing assays, blocking antibody experiments in vitro and in syngeneic mouse models Journal for immunotherapy of cancer Medium 32503945
2020 The NECTIN4 endo-domain (lacking extracellular region) translocates to the nucleus via physical interaction with IMPORTIN-α2 and activates DNA repair, while the ecto-domain (lacking signal peptide and cytoplasmic region) is expressed in the cytoplasm and specifically activates angiogenesis. Full-length NECTIN-4 modulates both processes. Domain-specific NECTIN-4 constructs overexpressed in 5-FU-resistant cervical cancer stem cells, co-immunoprecipitation with IMPORTIN-α2, nuclear fractionation, comet assay, γ-H2AX immunofluorescence, BER pathway assays, in vitro tube formation, CAM assay European journal of pharmacology Medium 32603697
2023 Nectin-4 plays a causative role in senescence-associated cell size enlargement via the Src family kinase (SFK)/PI3K/Rac1 pathway. Overexpression of Nectin-4 caused enlarged cell morphology resembling senescent cells; knockdown of Nectin-4 during DNA damage-induced senescence suppressed cell size increase without affecting senescence induction per se. Nectin-4 knockdown also induced apoptosis in senescent cells, and cell size was positively correlated with survival rate. Overexpression and knockdown of Nectin-4, pharmacological inhibition of SFK/PI3K/Rac1, single-cell tracking microscopy, flow cytometry for cell size, apoptosis assays Scientific reports Medium 38062106
2020 ERRα (estrogen-related receptor-α) transcriptionally activates NECTIN-4 by directly binding to the NECTIN-4 promoter, as shown by chromatin immunoprecipitation and dual-luciferase reporter assays. ERRα-induced gallbladder cancer cell proliferation and invasion were antagonized by Nectin-4 depletion. Nectin-4 depletion inhibited ERRα-induced PI3K/AKT pathway activation. Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, siRNA knockdown, overexpression, Western blot for PI3K/AKT pathway components, in vivo xenograft Cancer science Medium 32030850
2005 PICK-1 (protein interacting with C-kinase-1) directly interacts with nectins in a PDZ-domain-dependent manner and co-localizes with nectins at adherens junctions in epithelial cells, suggesting a role for PICK-1 in the regulation of nectin-based cell junctions. Co-immunoprecipitation, GST-pulldown, immunofluorescence co-localization in epithelial cells FEBS letters Low 15811349

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2016 Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer research 552 27013195
2011 Adherens junction protein nectin-4 is the epithelial receptor for measles virus. Nature 478 22048310
1999 Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. The Journal of cell biology 450 10225955
2011 Tumor cell marker PVRL4 (nectin 4) is an epithelial cell receptor for measles virus. PLoS pathogens 409 21901103
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2020 EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 278 32031899
2001 Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. The Journal of biological chemistry 272 11544254
2012 Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. Cell death and differentiation 262 23154388
2021 Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial. The Lancet. Oncology 230 33991512
2009 Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer research 225 19679554
2023 Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance. Clinical cancer research : an official journal of the American Association for Cancer Research 176 36534531
2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Science signaling 162 25468996
2010 Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker. American journal of clinical pathology 162 20959669
1998 The human poliovirus receptor related 2 protein is a new hematopoietic/endothelial homophilic adhesion molecule. Blood 151 9845526
2007 Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC cancer 149 17474988
2021 Heterogeneity in NECTIN4 Expression Across Molecular Subtypes of Urothelial Cancer Mediates Sensitivity to Enfortumab Vedotin. Clinical cancer research : an official journal of the American Association for Cancer Research 141 34108177
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2015 Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer. Journal of experimental & clinical cancer research : CR 137 25888293
2005 Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17. The Journal of biological chemistry 133 15784625
2021 Expression of Nectin-4 in Bladder Urothelial Carcinoma, in Morphologic Variants, and Nonurothelial Histotypes. Applied immunohistochemistry & molecular morphology : AIMM 131 33901032
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2017 Nectin-4: a new prognostic biomarker for efficient therapeutic targeting of primary and metastatic triple-negative breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology 124 27998973
2002 Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C-C'-C"-D beta-strands of the nectin1 V domain. The Journal of biological chemistry 118 12011057
2012 Nectin ectodomain structures reveal a canonical adhesive interface. Nature structural & molecular biology 109 22902367
2022 Management of Dermatologic Events Associated With the Nectin-4-directed Antibody-Drug Conjugate Enfortumab Vedotin. The oncologist 108 35274723
2020 Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity. Journal for immunotherapy of cancer 104 32503945
2013 A role for PVRL4-driven cell-cell interactions in tumorigenesis. eLife 104 23682311
2024 NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 101 38657187
2012 Nectin 4 is the epithelial cell receptor for measles virus. Trends in microbiology 100 22721863
2010 Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome. American journal of human genetics 97 20691405
2016 A novel PI3K/AKT signaling axis mediates Nectin-4-induced gallbladder cancer cell proliferation, metastasis and tumor growth. Cancer letters 92 26949052
2012 Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4. Nature structural & molecular biology 90 23202587
2017 Nectin-4 is a breast cancer stem cell marker that induces WNT/β-catenin signaling via Pi3k/Akt axis. The international journal of biochemistry & cell biology 82 28600142
2023 First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 76 37093191
2020 Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma. International journal of molecular sciences 76 32751328
2021 Nectin cell adhesion molecule-4 (NECTIN-4): A potential target for cancer therapy. European journal of pharmacology 72 34547246
2013 Characterization of ovine Nectin-4, a novel peste des petits ruminants virus receptor. Journal of virology 70 23388720
2017 Ectodomain shedding of the cell adhesion molecule Nectin-4 in ovarian cancer is mediated by ADAM10 and ADAM17. The Journal of biological chemistry 64 28232483
2022 The Anti-Nectin 4: A Promising Tumor Cells Target. A Systematic Review. Molecular cancer therapeutics 62 35131876
2021 Role of Nectin‑4 protein in cancer (Review). International journal of oncology 58 34664682
2022 BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors. Molecular cancer therapeutics 57 36112771
2011 The significance of Survivin and Nectin-4 expression in the prognosis of breast carcinoma. Folia histochemica et cytobiologica 57 21526486
2022 Overcoming Resistance to Anti-Nectin-4 Antibody-Drug Conjugate. Molecular cancer therapeutics 55 35534238
2022 Nectin-4-targeted immunoSPECT/CT imaging and photothermal therapy of triple-negative breast cancer. Journal of nanobiotechnology 55 35614462
2018 Cell clustering mediated by the adhesion protein PVRL4 is necessary for α6β4 integrin-promoted ferroptosis resistance in matrix-detached cells. The Journal of biological chemistry 54 29934307
2011 A secreted protein microarray platform for extracellular protein interaction discovery. Analytical biochemistry 53 21982860
2017 Nectin-4 promotes gastric cancer progression via the PI3K/AKT signaling pathway. Human pathology 52 29208564
2014 The tumor-associated marker, PVRL4 (nectin-4), is the epithelial receptor for morbilliviruses. Viruses 51 24892636
2018 The soluble nectin-4 ecto-domain promotes breast cancer induced angiogenesis via endothelial Integrin-β4. The international journal of biochemistry & cell biology 50 30056265
2017 The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate. Oncotarget 50 28038455
2015 The Nectin-4/Afadin Protein Complex and Intercellular Membrane Pores Contribute to Rapid Spread of Measles Virus in Primary Human Airway Epithelia. Journal of virology 50 25926640
2015 Characterization of human reflex tear proteome reveals high expression of lacrimal proline-rich protein 4 (PRR4). Proteomics 48 26173177
2014 Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer. Oncogenesis 48 25178039
2020 RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation. Proceedings of the National Academy of Sciences of the United States of America 47 32513696
2022 Development of Nectin4/FAP-targeted CAR-T cells secreting IL-7, CCL19, and IL-12 for malignant solid tumors. Frontiers in immunology 46 36479116
2019 Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse. Journal of cancer research and clinical oncology 45 31617074
2023 Assessment of PD-L1, TROP2, and nectin-4 expression in penile squamous cell carcinoma. Human pathology 42 37977513
2019 Autophagy induction by the pathogen receptor NECTIN4 and sustained autophagy contribute to peste des petits ruminants virus infectivity. Autophagy 42 31318632
2021 Nectin-4 promotes lymphangiogenesis and lymphatic metastasis in breast cancer by regulating CXCR4-LYVE-1 axis. Vascular pharmacology 39 33945869
2020 PARP inhibitor Veliparib (ABT-888) enhances the anti-angiogenic potentiality of Curcumin through deregulation of NECTIN-4 in oral cancer: Role of nitric oxide (NO). Cellular signalling 39 33373686
2019 Nanoquinacrine sensitizes 5-FU-resistant cervical cancer stem-like cells by down-regulating Nectin-4 via ADAM-17 mediated NOTCH deregulation. Cellular oncology (Dordrecht, Netherlands) 37 30603978
2013 The measles virus hemagglutinin β-propeller head β4-β5 hydrophobic groove governs functional interactions with nectin-4 and CD46 but not those with the signaling lymphocytic activation molecule. Journal of virology 37 23760251
2024 Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts. Histopathology 36 38196202
2020 NECTIN4 Expression in Extramammary Paget's Disease: Implication of a New Therapeutic Target. International journal of molecular sciences 36 32824340
2016 Expression and clinical significance of Nectin-4 in hepatocellular carcinoma. OncoTargets and therapy 36 26793002
2015 SLAM- and nectin-4-independent noncytolytic spread of canine distemper virus in astrocytes. Journal of virology 35 25787275
2019 NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT. Cancer management and research 34 31114323
2019 Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis. Scientific reports 34 31831814
2016 Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys. Molecular imaging and biology 34 27122234
2005 PICK-1: a scaffold protein that interacts with Nectins and JAMs at cell junctions. FEBS letters 34 15811349
2022 Nectin-4: a Novel Therapeutic Target for Skin Cancers. Current treatment options in oncology 33 35312963
2014 Nectin-4 mutations causing ectodermal dysplasia with syndactyly perturb the rac1 pathway and the kinetics of adherens junction formation. The Journal of investigative dermatology 33 24577405
2023 An Analysis of Nectin-4 (PVRL4) in Penile Squamous Cell Carcinoma. European urology open science 31 36660545
2021 NECTIN4: A Novel Therapeutic Target for Melanoma. International journal of molecular sciences 31 33478111
2021 Nectin Cell Adhesion Molecule 4 (NECTIN4) Expression in Cutaneous Squamous Cell Carcinoma: A New Therapeutic Target? Biomedicines 31 33808400
2015 p63-dependent and independent mechanisms of nectin-1 and nectin-4 regulation in the epidermis. Experimental dermatology 31 25387952
2012 Canine distemper virus with the intact C protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor. Virology 31 23174504
2023 Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E-based Antibody-Drug Conjugate for Treatment of Nectin-4-expressing Cancers. Molecular cancer therapeutics 30 37196158
2017 Measles Virus Enters Breast and Colon Cancer Cell Lines through a PVRL4-Mediated Macropinocytosis Pathway. Journal of virology 29 28250131
2024 Therapeutic prospects of nectin-4 in cancer: applications and value. Frontiers in oncology 27 38606099
2022 Nectin-4 is widely expressed in head and neck squamous cell carcinoma. Oncotarget 27 36268557
2020 Estrogen-related receptor-α promotes gallbladder cancer development by enhancing the transcription of Nectin-4. Cancer science 27 32030850
2014 The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread. Virology 27 24725937
2014 Characterization of lacrimal proline-rich protein 4 (PRR4) in human tear proteome. Proteomics 27 24782455
2024 Nectin-4-directed antibody-drug conjugates (ADCs): Spotlight on preclinical and clinical evidence. Life sciences 26 39002610
2020 Recombinant SLAMblind Measles Virus Is a Promising Candidate for Nectin-4-Positive Triple Negative Breast Cancer Therapy. Molecular therapy oncolytics 26 33145396
2014 Use of SLAM and PVRL4 and identification of pro-HB-EGF as cell entry receptors for wild type phocine distemper virus. PloS one 26 25171206
2020 Nanoformulated quinacrine regulates NECTIN-4 domain specific functions in cervical cancer stem cells. European journal of pharmacology 25 32603697
2019 Enfortumab Vedotin, a fully human monoclonal antibody against Nectin 4 conjugated to monomethyl auristatin E for metastatic urothelial Carcinoma. Expert opinion on investigational drugs 25 31526130
2011 Mutation in PVRL4 gene encoding nectin-4 underlies ectodermal-dysplasia-syndactyly syndrome (EDSS1). Journal of human genetics 25 21346770
2020 Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4. International journal of molecular sciences 24 32629816
2024 Translational PET Imaging of Nectin-4 Expression in Multiple Different Cancers with 68Ga-N188. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 22 38719240
2020 Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. The Annals of pharmacotherapy 22 32945172
2019 Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior? Wiener klinische Wochenschrift 21 31440821
2025 Spatial Expression of HER2, NECTIN4, and TROP-2 in Muscle-Invasive Bladder Cancer and Metastases: Implications for Pathological and Clinical Management. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 18 40086591
2024 Near-infrared photoimmunotherapy targeting Nectin-4 in a preclinical model of bladder cancer. Cancer letters 18 38272345
2024 A potential strategy for bladder cancer treatment: inhibiting autophagy to enhance antitumor effects of Nectin-4-MMAE. Cell death & disease 18 38664366
2024 A humanized trivalent Nectin-4-targeting nanobody drug conjugate displays potent antitumor activity in gastric cancer. Journal of nanobiotechnology 18 38755613
2022 Nectin-4 promotes osteosarcoma progression and metastasis through activating PI3K/AKT/NF-κB signaling by down-regulation of miR-520c-3p. Cancer cell international 18 35953862
2019 Functional characterization of seven-band grouper immunoglobulin like cell adhesion molecule, Nectin4 as a cellular receptor for nervous necrosis virus. Fish & shellfish immunology 17 31404634
2014 The diagnostic efficacy of nectin 4 expression in ovarian cancer patients. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 17 25019423
2023 Scratching the Surface: NECTIN-4 as a Surrogate for Enfortumab Vedotin Resistance. Clinical cancer research : an official journal of the American Association for Cancer Research 16 36749325
2023 An iodine‑labelled Antibody-drug conjugate PET probe for noninvasive monitoring of Nectin-4 expression in urothelial carcinoma. International journal of pharmaceutics 16 38160990
2018 Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study. BMC medical genetics 16 30217189
2024 Biomarkers of Response to Anti-NECTIN4 Antibody-Drug Conjugate Enfortumab Vedotin in Urothelial Cancer. European urology focus 15 38631991
2022 CircRNA PRH1-PRR4 stimulates RAB3D to regulate the malignant progression of NSCLC by sponging miR-877-5p. Thoracic cancer 15 35076987
2014 A novel homozygous nonsense mutation in the PVRL4 gene and expansion of clinical spectrum of EDSS1. Annals of human genetics 15 25529316
2025 Pilot Study of Nectin-4-Targeted PET Imaging Agent 68Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 14 39947908
2022 TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma. Cancers 14 35158847
2025 Bulumtatug Fuvedotin (BFv, 9MW2821), a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open-label, multicenter, phase I/II study. Annals of oncology : official journal of the European Society for Medical Oncology 13 40288679
2022 Discovery and Optimization of a Synthetic Class of Nectin-4-Targeted CD137 Agonists for Immuno-oncology. Journal of medicinal chemistry 13 35819182
2019 Nectin-4 and p63 immunohistochemical expression in canine prostate tumourigenesis. Veterinary and comparative oncology 13 30767361
2016 Identification of a naturally processed HLA-A*02:01-restricted CTL epitope from the human tumor-associated antigen Nectin-4. Cancer immunology, immunotherapy : CII 13 27514672
2024 Nectin-4 Positivity in Genitourinary Malignancies: A Systematic Review. JCO precision oncology 12 39626158
2021 Expressions of PD-L1 and Nectin-4 in urothelial cancer patients treated with pembrolizumab. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 12 34687441
2025 Nectin-4 expression patterns and therapeutics in oncology. Cancer letters 11 40209851
2024 TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma. Pathologica 11 38482675
2022 Heterogenous NECTIN4 expression in urothelial high-risk non-muscle-invasive bladder cancer. Virchows Archiv : an international journal of pathology 11 35484425
2024 Effects of PEGylation on Imaging Contrast of 68Ga-Labeled Bicyclic Peptide PET Probes Targeting Nectin-4. Molecular pharmaceutics 10 39069891
2024 Targeted therapeutic strategies for Nectin-4 in breast cancer: Recent advances and future prospects. Breast (Edinburgh, Scotland) 10 39577073
2023 Nectin-4: a Tumor Cell Target and Status of Inhibitor Development. Current oncology reports 10 36696077
2023 Nectin-4 has emerged as a compelling target for breast cancer. European journal of pharmacology 10 38059449
2023 Nectin-4 regulates cellular senescence-associated enlargement of cell size. Scientific reports 9 38062106