alpha2,6-Sialyltransferase gene transfection into a human glioma cell line (U373 MG) results in decreased invasivity.
Glycosyltransferase gene transfection into cell lines has been an approach used successfully to elucidate the functional role of cell surface glycoconjugates. We have transfected the rat CMP-NeuAc:Galbeta1,4GlcNAc alpha2,6-sialyltransferase (EC 2.4.99.1) gene into a human, tumorigenic, glioma cell line, U373 MG. This transfection led to a marked inhibition of invasivity, alterations in adhesivity to fibronectin and collagen matrices, and inappropriately sialylated alpha3beta1 integrin. Adhesion-mediated protein tyrosine phosphorylation was reduced in the transfectants despite increased expression of focal adhesion kinase, p125fak. Furthermore, the transfectants showed a distinct cell morphology, an increased number of focal adhesion sites, and different sensitivity to cytochalasin D treatment than control U373 MG cells. These results suggest that inappropriate sialylation of cell surface glycoconjugates, such as integrins, can change focal adhesion as well as adhesion-mediated signal transduction and block glioma cell invasivity in vitro.
Yamamoto
H
H
Chicago Institute for Neurosurgery and Neuroresearch, Illinois, U.S.A.
Kaneko
Y
Y
Rebbaa
A
A
Bremer
E G
EG
Moskal
J R
JR
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005910:Glioma; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039201:Integrin alpha3beta1; D016023:Integrins; D017474:Receptors, Laminin; D012794:Sialic Acids; D014443:Tyrosine; D003094:Collagen; D012799:Sialyltransferases; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496052:Ptk2 protein, rat; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase