Glycosynaptic microdomains controlling tumor cell phenotype through alteration of cell growth, adhesion, and motility |
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Authors: | Sen-itiroh Hakomori |
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Affiliation: | Division of Biomembrane Research, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA Departments of Pathobiology and Global Health, University of Washington, Seattle, WA 98195, USA |
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Abstract: | Glycosphingolipids (GSLs) GM3 (NeuAcα3Galβ4Glcβ1Cer) and GM2 (GalNAcβ4[NeuAcα3]Galβ4Glcβ1Cer) inhibit (i) cell growth through inhibition of tyrosine kinase associated with growth factor receptor (GFR), (ii) cell adhesion/motility through inhibition of integrin-dependent signaling via Src kinases, or (iii) both cell growth and motility by blocking “cross-talk” between integrins and GFRs. These inhibitory effects are enhanced when GM3 or GM2 are in complex with specific tetraspanins (TSPs) (CD9, CD81, CD82). Processes (i)-(iii) occur through specific organization of GSLs with key molecules (TSPs, caveolins, GFRs, integrins) in the glycosynaptic microdomain. Some of these processes are shared with epithelial-mesenchymal transition induced by TGFβ or under hypoxia, particularly that associated with cancer progression. |
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Keywords: | Csk, C-terminal Src kinase EMT, epithelial-mesenchymal transition FGFR, fibroblast growth factor receptor FN, fibronectin GFR, growth factor receptor Gg3, GalNAcβ4Galβ4Glcβ1Cer (gangliotriaosylceramide) Gg4, Galβ3GalNAcβ4Galβ4Glcβ1Cer (gangliotetraosylceramide) GM2, GalNAcβ4[NeuAcα3]Galβ4Glcβ1Cer GM3, NeuAcα3Galβ4Glcβ1Cer GSL, glycosphingolipid LN5, laminin-5 TSP, tetraspanin |
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