The syndecans, a family of four cell surface heparan sulfate-decorated receptors, are cell adhesion receptors and regulators of signaling by growth factors/growth factor receptors. Our work focuses on mechanisms by which they regulate the invasion and survival of tumors cells, as well as vascular endothelial cells undergoing angiogenesis.
We have study several mechanisms by which syndecans act as organizers of receptor signaling at the tumor cell surface. In each of these cases, the syndecan captures an integrin (a matrix adhesion receptor) and a receptor tyrosine kinase (e.g., insulin-like growth factor receptor (IGF-1R), vascular endothelial cell growth factor receptor (VEGFR2)) epidermal growth factor receptor (EGFR) and the EGFR family member HER2) via a site in the syndecan extracellular domain. Capture of the receptors is essential for signaling by the receptor tyrosine kinase, and for activation of the integrin. We have developed peptides (called “synstatin” or SSTNs) that mimic the capture site in the syndecan and compete for receptor capture. This inhibitory peptides block tumor proliferation and survival in vitro and in vivo, and also block angiogenesis. The laboratory is currently working to analyze how these mechanisms work, their signaling pathways, and the efficacy as potential cancer therapies.
Current lab members include:
- Benjamin L. Allen, Cellular and Molecular Biology graduate student
- Kyle J. McQuade, Cellular and Molecular Biology graduate student
- DeannaLee Beauvais, Molecular and Cellular Pharmacology post-doc
- Yan Ji, Cellular and Molecular Pathology graduate student
- Tristana Von Will, Cancer Biology graduate student
- Xinping Yue, Postdoctoral fellow
- Andrea McWhorter, Research Specialist
- Jennifer Bowers, undergraduate
- Ashley Hansen, undergraduate
Honors & Awards
- 2016 – Invited Speaker, Gordon Conference on Proteoglycans
- 2014 – Speaker and Co-organizer, International meeting on “Syndecans in Cell Regulation and Disease,” Leuven, Belgium
- 2006 – Chair, Proteoglycan Gordon Conference
- 2004 – Vice-chair, Proteoglycan Gordon Conference
- 2004 – Plenary Session Chair and Speaker, American Society for Matrix Biology
Recent invited talks:
- Gordon Conference on Signal Transduction by Engineered Extracellular Matrices
- Proteoglycan Gordon Conference
- American Society for Matrix Biology, Inaugural annual symposium, Houston, Texas,
- American Society for Biochemistry and Molecular Biology, Annual Meeting, San Diego CA.
- International Symposium on Heparan Sulfate Proteoglycans, Kyoto, Japan
- FASEB conference on Muscle Satellite and Stem Cells, Tuscon, AZ
- Wang, H., Jin, H., Beauvais, D.M. and Rapraeger, A.C. (2014). 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. J. Biol. Chem., 289: 30318-30332.
- Rapraeger, A.C., Ell, B.J., Roy, M., Li, X., Morrison, O.R., Thomas, G.M., and Beauvais, D.M. (2013). VE-cadherin stimulates syndecan-1 coupled IGF1R and cross-talk between αvβ3 integirn and VEGFR2 at the onset of endothelial cell dissemination during angiogenesis. FEBS J., 280: 2194-2206.
- Rapraeger, A.C. (2013). Synstatin: a selective inhibitor of the syndecan-1-coupled IGF1R-αvβ3 integrin complex in tumorigenesis and angiogenesis. FEBS J., 280: 2207-2215
- Beauvais, D.M. and Rapraeger, A.C. (2010). Syndecan-1 Couples the Insulin-like Growth Factor-1 Receptor To Inside-out Integrin Activation. J. Cell Sci., 123: 3796-3807.
- Beauvais, D.M, Ell, B.J, McWhorter, A.R. and Rapraeger, A.C. (2009). Syndecan-1-regulates αvβ3 and αvβ5 integrin activation during angiogenesis and is blocked by synstatin. J. Exp. Med. 206: 691-705.