ArticleJournal of cell science2010
Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation.
Article in Journal of cell science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 113 citations in OpenAlex.
- Syndecan-2 enhances invasive motility in colon cancer cells via a laminin-332-integrin α6β1 axis.The Journal of biological chemistry · 2026Article
- SSTNSignal transduction and targeted therapy · 2026Article
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- Targeting Prostate Cancer Cells Using Anti-Sortilin and Anti-Syndecan-1 Antibody Drug Conjugates.International journal of molecular sciences · 2025Article
- Matrix: a complex amalgam of structures and functions in tumor microenvironment.FEBS open bio · 2025Review
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- SDC1 is a critical transmembrane proteoglycan in breast cancer.World journal of surgical oncology · 2025Review
- Impact of mesenchymal stromal cell-derived vesicular cargo on B-cell acute lymphoblastic leukemia progression.Blood advances · 2023Article
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- Inhibiting IGF1R-mediated Survival Signaling in Head and Neck Cancer with the Peptidomimetic SSTNCancer research communications · 2023Article
- The Role of Molecular and Hormonal Factors in Obesity and the Effects of Physical Activity in Children.International journal of molecular sciences · 2022Review
- The fibrogenic niche in kidney fibrosis: components and mechanisms.Nature reviews. Nephrology · 2022Review
- Review
- Targeting syndecan-1: new opportunities in cancer therapy.American journal of physiology. Cell physiology · 2022Review
- 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
- Characterization of glucose metabolism in breast cancer to guide clinical therapy.Frontiers in surgery · 2022Article
- Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans.Matrix biology plus · 2021Article
- Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Convergent chemoenzymatic synthesis and biological evaluation of a heparan sulfate proteoglycan syndecan-1 mimetic.Chemical communications (Cambridge, England) · 2021Article
- Syndecans and Pancreatic Ductal Adenocarcinoma.Biomolecules · 2021Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Syndecan-1 (Sdc1) engages and activates the αvβ3 (and/or αvβ5) integrin when clustered in human carcinoma and endothelial cells. Although the engagement is extracellular, the activation mechanism is cytoplasmic. This talin-dependent, inside-out signaling pathway is activated downstream of the insulin-like growth factor-1 receptor (IGF1R), whose kinase activity is triggered by Sdc1 clustering. In vitro binding assays using purified receptors suggest that association of the Sdc1 ectodomain with the integrin provides a 'docking face' for IGF1R. IGF1R docking and activation of the associated integrin is blocked by synstatin (SSTN(92-119)), a peptide derived from the integrin engagement site in Sdc1. IGF1R colocalizes with αvβ3 integrin and Sdc1 in focal contacts, but fails to associate with or activate the integrin in cells either lacking Sdc1 or expressing Sdc1(Δ67-121), a mutant that is unable to form the Sdc1-integrin-IGF1R ternary complex. Integrin activation is also blocked by IGF1R inhibitors or by silencing IGF1R or talin expression with small-interfering RNAs (siRNAs). In both cases, expression of the constitutively active talin F23 head domain rescues integrin activation. We recently reported that SSTN(92-119) blocks angiogenesis and impairs tumor growth in mice, therefore this Sdc1-mediated integrin regulatory mechanism might be a crucial regulator of disease processes known to rely on these integrins, including tumor cell metastasis and tumor-induced angiogenesis.
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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 OpenQuestion graph.