Glypicans - A Brief Review
Keywords:Glypican, Hedgehogs, BMP.
Glypicans (GPCs) are a family of proteoglycans that are bound to the cell surface by a glycosyl-phosphatidylinositol anchor. Six glypicans have been found in the mammalian genome (GPC1 to GPC6). Glypicans can be released from the cell surface by a lipase called Notum, and most of them are subjected to endoproteolytic cleavage by furin-like convertases. In vivo evidence published so far indicates that the main function of membrane-attached glypicans is to regulate the signaling of Wnts, Hedgehogs, fibroblast growth factors and bone morphogenetic proteins (BMPs). Surprisingly, the regulatory activity of glypicans in the Wnt, Hedgehog and BMP signaling pathways is only partially dependent on the heparan sulfate chains. It is obvious that our knowledge of glypican functions is still very limited despite the recent advances. A better understanding of these functions will make a significant contribution to the study of signaling pathways that play a very important role in developmental morphogenesis and several human diseases, including cancer.
Torisu Y, Watanabe A, Nonaka A, et al. Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by β‐catenin/TCF. Canc Sci 2008; 99(6): 1139-1146. https://doi.org/10.1111/j.1349-7006.2008.00814.x DOI: https://doi.org/10.1111/j.1349-7006.2008.00814.x
De Cat B, Muyldermans S-Y, Coomans C, et al. Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements. J Cell Biol 2003; 163(3): 625-635. https://doi.org/10.1083/jcb.200302152 DOI: https://doi.org/10.1083/jcb.200302152
Filmus J, Capurro M. The glypican family. In: Karamanos, Nikos K. (Ed.), Extracellular Matrix: Pathobiology and Signaling. De Gruyter, Berlin/Boston, 2012; pp. 209-220. DOI: https://doi.org/10.1515/9783110258776.209
Filmus J, et al. Glypicans. Genome Biol 2008; 9: 224. https://doi.org/10.1186/gb-2008-9-5-224
Li F, et al. Glypican-5 stimulates rhabdomyosarcoma cell proliferation by activating Hedgehog signaling. J Cell Biol 2011; 192: 691-704. https://doi.org/10.1083/jcb.201008087 DOI: https://doi.org/10.1083/jcb.201008087
Bologna-Molina R, Mosqueda-Taylor A, Molina‑Frechero N. Differential expression of glypican-1 in ameloblastoma variants. Appl Immunohistochem Mol Morphol 2015; 23: 153-60. https://doi.org/10.1097/PAI.0000000000000042 DOI: https://doi.org/10.1097/PAI.0000000000000042
Mendes RB, Dias RB, Figueiredo AL, Gurgel CA, Santana Filho M, Melo LA, et al. Glypican-3 distinguishes aggressive from non-aggressive odontogenic tumors: A preliminary study. J Oral Pathol Med 2017; 46: 297-300. https://doi.org/10.1111/jop.12501 DOI: https://doi.org/10.1111/jop.12501
Capurro M, Xiang YY, Lobe C, Filmus J. Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling. Cancer Res 2005; 6655: 6245-6254. https://doi.org/10.1158/0008-5472.CAN-04-4244 DOI: https://doi.org/10.1158/0008-5472.CAN-04-4244
Capurro MI, Xu P, Shi W, Li F, Jia A, Filmus J. Glypican-3 inhibits hedgehog signaling during development by competing with Patched for Hedgehog binding. Dev Cell 2008; 1144: 700-711. https://doi.org/10.1016/j.devcel.2008.03.006 DOI: https://doi.org/10.1016/j.devcel.2008.03.006
Lum L, Yao S, Mozer B, Rovescalli A, Von Kessler D, Nirenberg M, Beachy PA. Identification of hedgehog pathway components by RNAi in Drosophila cultured cells. Science 2003; 229999: 2039-2045. https://doi.org/10.1126/science.1081403 DOI: https://doi.org/10.1126/science.1081403
Song HH, Shi W, Filmus J. OCI-5/rat glypican-3 binds to fibroblast growth factor-2 but not to insulin -like growth factor-2. J Biol Chem 1997; 227722: 7574-7577. https://doi.org/10.1074/jbc.272.12.7574 DOI: https://doi.org/10.1074/jbc.272.12.7574
Veugelers M, De Cat B, Ceulemans H, Bruystens AM, Coomans C,Durr J, Vermeesch J, Marynen P, David G. Glypican-6, a new member of the glypican family of cell surface proteoglycans. J Biol Chem 1999; 227744: 26968-26977. https://doi.org/10.1074/jbc.274.38.26968 DOI: https://doi.org/10.1074/jbc.274.38.26968
Topczewsky J, Sepich DS, Myers DC, Walker C, Amores A, Lele Z, Hammerschmidt M, Postlethwait J, Solnica-Krezel L. The zebrafish glypican Knypek controls cell polarity during gastrulation movements of convergent extension. Dev Cell 2001; 11: 251-264. https://doi.org/10.1016/S1534-5807(01)00005-3 DOI: https://doi.org/10.1016/S1534-5807(01)00005-3