Glycosynaptic microdomains controlling tumor cell phenotype through alteration of cell growth, adhesion, and motility.
Glycosphingolipids (GSLs) GM3 (NeuAcalpha3Galbeta4Glcbeta1Cer) and GM2 (GalNAcbeta4[NeuAcalpha3]Galbeta4Glcbeta1Cer) 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 TGFbeta or under hypoxia, particularly that associated with cancer progression.
Hakomori
Sen-itiroh
SI
Division of Biomembrane Research, Pacific Northwest Research Institute, Seattle, WA 98122, USA. hakomori@u.washington.edu
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006028:Glycosphingolipids / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype
D006028:Glycosphingolipids; D008565:Membrane Proteins