A tumor-associated glycosylation change in the glucose transporter GLUT1 controlled by tumor suppressor function in human cell hybrids.
Studies of human cell hybrids have provided evidence that the tumorigenicity of a cervical carcinoma (HeLa) is under the control of a putative tumor suppressor on chromosome 11. Using these human cell hybrids, we found a tumor-associated glycosylation change in the glucose transporter GLUT1, which is an N-linked glycoprotein at the plasma membrane. The non-tumorigenic HeLa x fibroblast cell hybrid CGL1 and the normal diploid fibroblast WI38 expressed the 50-55 kDa GLUT1, whereas in a tumorigenic segregant hybrid, CGL4, as well as in parental HeLa cells, GLUT1 glycosylation was altered and its molecular mass was about 70 kDa. However, the altered GLUT1 glycosylation was not observed in SV40-transformed WI38 cells, suggesting a correlation between this glycosylation change and a putative tumor suppressor function. Further investigations using glycosidases, glycosylation inhibitors and lectin-affinity chromatography demonstrated that the tumor-associated glycosylation change in GLUT1 was mainly due to the increase in N-acetyl-lactosamine repeats in the N-linked oligosaccharides. In accordance with the altered glycosylation, affinity for 2-deoxyglucose in the tumorigenic CGL4 cells increased 2-fold, but there was little change in the Vmax. These results suggest there may be a functional role for the modulation by glycosylation of GLUT1 in the tumorigenic behavior of CGL4 and HeLa cells.
Kitagawa
T
T
Department of Biochemistry and Cell Biology, National Institute of Health, Tokyo, Japan.
Tsuruhara
Y
Y
Hayashi
M
M
Endo
T
T
Stanbridge
E J
EJ
D001692:Biological Transport / Q000502:physiology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002880:Chromosomes, Human, Pair 11; D005260:Female; D016147:Genes, Tumor Suppressor; D005947:Glucose / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D009844:Oligosaccharides; C495677:SLC2A1 protein, human; D005947:Glucose