ArticleScientific reports2019
Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Combining an anti-HER2 antibody-drug conjugate with an anti-nectin-4 antibody-drug conjugate enhances efficacy in breast cancer and gastric cancer models.Cancer cell international · 2026Article
- Transfer factor alleviates bovine mastitis and protects mammary epithelial barrier via the TAK1/NF-κB/MLCK signaling axis.Journal of animal science · 2026Article
- Necl-4/CADM4 regulates GABAergic synaptic strength on GABAergic inhibitory neurons via ErbB4 activation and prevents neuronal impairments.Molecular neurobiology · 2025Article
- Nectin4-targeted molecular imaging in solid tumors: Current status and future perspectives.View (Beijing, China) · 2025Article
- Assessing the expression of Nectin-4 in solid tumors by immunohistochemistry - what do we know?Histology and histopathology · 2025Review
- Emerging evidence of targeting non-oncogenic drivers for gastric cancer: Claudin18.2 and beyond.Therapeutic advances in medical oncology · 2025Review
- Unlocking the potential of antibody-drug conjugates in cervical cancer: emerging targets and clinical trials.Frontiers in pharmacology · 2025Review
- STAT3: Key targets of growth-promoting receptor positive breast cancer.Cancer cell international · 2024Review
- Ocular adverse events associated with antibody-drug conjugates: a comprehensive pharmacovigilance analysis.Frontiers in immunology · 2024Article
- Therapeutic prospects of nectin-4 in cancer: applications and value.Frontiers in oncology · 2024Review
- Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E-based Antibody-Drug Conjugate for Treatment of Nectin-4-expressing Cancers.Molecular cancer therapeutics · 2023Article
- Future potential targets of antibody-drug conjugates in breast cancer.Breast (Edinburgh, Scotland) · 2023Review
- Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer with Mismatch Repair Impairment.Cancers · 2023Article
- Nectins and Nectin-like Molecules in Colorectal Cancer: Role in Diagnostics, Prognostic Values, and Emerging Treatment Options: A Literature Review.Diagnostics (Basel, Switzerland) · 2022Review
- Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021.Journal of hematology & oncology · 2022Review
- Nectin-4: a Novel Therapeutic Target for Skin Cancers.Current treatment options in oncology · 2022Review
- Antibody-Drug Conjugates in Urothelial Carcinoma: A New Therapeutic Opportunity Moves from Bench to Bedside.Cells · 2022Review
- Nectin-2 in general and in the brain.Molecular and cellular biochemistry · 2022Review
- Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma.Expert opinion on biological therapy · 2021Review
- Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling.Cells · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nectin-4 cell adhesion molecule and ErbB2 tyrosine kinase receptor are upregulated in many cancers, including breast cancer, and promote cancer cell proliferation and metastasis. Using human breast cancer cell lines T47D and SUM190-PT, in which both nectin-4 and ErbB2 were upregulated, we showed here that nectin-4 cis-interacted with ErB2 and enhanced its dimerization and activation, followed by the activation of the phosphoinositide 3-kinase-AKT signalling pathway for DNA synthesis. The third immunoglobulin-like domain of nectin-4 cis-interacted with domain IV of ErbB2. This region differs from the trastuzumab-interacting region but is included in the trastuzumab-resistant splice variants of ErbB2, p95-ErbB2 and ErbB2ΔEx16. Nectin-4 also cis-interacted with these trastuzumab-resistant splice variants and enhanced the activation of the phosphoinositide 3-kinase-AKT signalling pathway for DNA synthesis. In addition, nectin-4 enhanced the activation of the p95-ErbB2-induced JAK-STAT3 signalling pathway, but not the ErbB2- or ErbB2ΔEx16-induced JAK-STAT3 signalling pathway. These results indicate that nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants and enhances the activation of these receptors and downstream signalling pathways in a novel mechanism.
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