ArticleThe Journal of biological chemistry2015
Syndecan-1 and Syndecan-4 Capture Epidermal Growth Factor Receptor Family Members and the α3β1 Integrin Via Binding Sites in Their Ectodomains: NOVEL SYNSTATINS PREVENT KINASE CAPTURE AND INHIBIT α6β4-INTEGRIN-DEPENDENT EPITHELIAL CELL MOTILITY.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
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- 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
- PDZ scaffolds regulate extracellular vesicle production, composition, and uptake.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Impact of mesenchymal stromal cell-derived vesicular cargo on B-cell acute lymphoblastic leukemia progression.Blood advances · 2023Article
- Thy-1 (CD90)-regulated cell adhesion and migration of mesenchymal cells: insights into adhesomes, mechanical forces, and signaling pathways.Frontiers in cell and developmental biology · 2023Review
- Inhibiting IGF1R-mediated Survival Signaling in Head and Neck Cancer with the Peptidomimetic SSTNCancer research communications · 2023Article
- Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer.Theranostics · 2023Article
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- 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
- Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans.Matrix biology plus · 2021Article
- Article
- Syndecan-1 (CD138), Carcinomas and EMT.International journal of molecular sciences · 2021Review
- Syndecan-4 as a Pathogenesis Factor and Therapeutic Target in Cancer.Biomolecules · 2021Review
- Syndecans and Pancreatic Ductal Adenocarcinoma.Biomolecules · 2021Review
- Syndecan receptors: pericellular regulators in development and inflammatory disease.Open biology · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The α6β4 integrin is known to associate with receptor tyrosine kinases when engaged in epithelial wound healing and in carcinoma invasion and survival. Prior work has shown that HER2 associates with α6β4 integrin and syndecan-1 (Sdc1), in which Sdc1 engages the cytoplasmic domain of the β4 integrin subunit allowing HER2-dependent motility and carcinoma cell survival. In contrast, EGFR associates with Sdc4 and the α6β4 integrin, and EGFR-dependent motility depends on cytoplasmic engagement of β4 integrin with Sdc4. However, how HER2 and EGFR assimilate into a complex with the syndecans and integrin, and why kinase capture is syndecan-specific has remained unknown. In the present study, we demonstrate that HER2 is captured via a site, comprised of amino acids 210-240, in the extracellular domain of human Sdc1, and EGFR is captured via an extracellular site comprised of amino acids 87-131 in human Sdc4. Binding assays using purified recombinant proteins demonstrate that the interaction between the EGFR family members and the syndecans is direct. The α3β1 integrin, which is responsible for the motility of the cells, is captured at these sites as well. Peptides based on the interaction motifs in Sdc1 and Sdc4, called synstatins (SSTN210-240 and SSTN87-131) competitively displace the receptor tyrosine kinase and α3β1 integrin from the syndecan with an IC50 of 100-300 nm. The syndecans remain anchored to the α6β4 integrin via its cytoplasmic domain, but the activation of cell motility is disrupted. These novel SSTN peptides are potential therapeutics for carcinomas that depend on these HER2- and EGFR-coupled mechanisms for their invasion and survival.
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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 OpenQuestion graph.