ArticleThe Journal of biological chemistry2014
Cytoplasmic domain interactions of syndecan-1 and syndecan-4 with α6β4 integrin mediate human epidermal growth factor receptor (HER1 and HER2)-dependent motility and survival.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Syndecan-4 in microglia mediates ischemic stroke-induced mitochondrial dysfunction and blood-brain barrier damage by interacting with Dishevelled.Scientific reports · 2026Article
- Differential Impacts on Proteoglycan Expression in the Response to Lens Wounding in Reparative and Pro-fibrotic Microenvironments.Proteoglycan research · 2025Article
- Expression-based selection identifies a microglia-tropic AAV capsid for direct and CSF routes of administration in mice.bioRxiv : the preprint server for biology · 2024Article
- Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease.Biomolecules · 2024Review
- PDZ scaffolds regulate extracellular vesicle production, composition, and uptake.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Revisiting the Syndecans: Master Signaling Regulators with Prognostic and Targetable Therapeutic Values in Breast Carcinoma.Cancers · 2023Review
- Inhibiting IGF1R-mediated Survival Signaling in Head and Neck Cancer with the Peptidomimetic SSTNCancer research communications · 2023Article
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- Signaling Pathways Associated with Chronic Wound Progression: A Systems Biology Approach.Antioxidants (Basel, Switzerland) · 2022Article
- Plasma membrane proteoglycans syndecan-2 and syndecan-4 engage with EGFR and RON kinase to sustain carcinoma cell cycle progression.The Journal of biological chemistry · 2022Article
- Article
- Syndecan-4 in Tumor Cell Motility.Cancers · 2021Review
- Syndecan-4 as a Pathogenesis Factor and Therapeutic Target in Cancer.Biomolecules · 2021Review
- Integrin Regulation in Immunological and Cancerous Cells and Exosomes.International journal of molecular sciences · 2021Review
- Syndecans and Their Synstatins: Targeting an Organizer of Receptor Tyrosine Kinase Signaling at the Cell-Matrix Interface.Frontiers in oncology · 2021Review
- A stem cell reporter based platform to identify and target drug resistant stem cells in myeloid leukemia.Nature communications · 2020Article
- Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression.International journal of molecular sciences · 2020Review
- Interplay between Cell-Surface Receptors and Extracellular Matrix in Skin.Biomolecules · 2020Review
- Tetraspanin-6 negatively regulates exosome production.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Genetic Deletion ofNutrients · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Epithelial cells are highly dependent during wound healing and tumorigenesis on the α6β4 integrin and its association with receptor tyrosine kinases. Previous work showed that phosphorylation of the β4 subunit upon matrix engagement depends on the matrix receptor syndecan (Sdc)-1 engaging the cytoplasmic domain of the β4 integrin and coupling of the integrin to human epidermal growth factor receptor-2 (HER2). In this study, HER2-dependent migration activated by matrix engagement is compared with migration stimulated by EGF. We find that whereas HER2-dependent migration depends on Sdc1, EGF-dependent migration depends on a complex consisting of human epidermal growth factor receptor-1 (HER1, commonly known as EGFR), α6β4, and Sdc4. The two syndecans recognize distinct sites at the extreme C terminus of the β4 integrin cytoplasmic domain. The binding motif in Sdc1 is QEEXYX, composed in part by its syndecan-specific variable (V) region and in part by the second conserved (C2) region that it shares with other syndecans. A cell-penetrating peptide containing this sequence competes for HER2-dependent epithelial migration and carcinoma survival, although it is without effect on the EGFR-stimulated mechanism. β4 mutants bearing mutations specific for Sdc1 and Sdc4 recognition act as dominant negative mutants to block cell spreading or cell migration that depends on HER2 or EGFR, respectively. The interaction of the α6β4 integrin with the syndecans appears critical for it to be utilized as a signaling platform; migration depends on α3β1 integrin binding to laminin 332 (LN332; also known as laminin 5), whereas antibodies that block α6β4 binding are without effect. These findings indicate that specific syndecan family members are likely to have key roles in α6β4 integrin activation by receptor tyrosine kinases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.