Motility inhibition and apoptosis are induced by metastasis-suppressing gene product CD82 and its analogue CD9, with concurrent glycosylation.
Metastasis-suppressing gene product CD82 and its analogue CD9 are considered to suppress the malignancy of various human cancers, although the rationale for this effect is unknown. The present study addresses phenotypic changes in Chinese hamster ovary mutant cell line ldlD deficient in UDP-Glc 4-epimerase and expressing CD82 or CD9 by cDNA transfection. Only CD82- or CD9-expressing cells grown in Gal-supplemented medium showed reduced motility and massive cell death, which are characteristic of apoptosis, after a latent period. Under this condition, endogenous GM3 synthesis was observed as a common factor, and N-glycosylation occurred at a high level in CD82 and to a lesser extent in CD9. Thus, the malignancy-suppressing effect of CD82 or CD9 is based partially on cell motility inhibition and apoptosis induction promoted by concurrent GM3 synthesis and N-glycosylation.
Ono
M
M
Pacific Northwest Research Institute, Seattle, Washington 98122, USA.
Handa
K
K
Withers
D A
DA
Hakomori
S
S
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics*; D016466:CHO Cells / Q000201:enzymology; D002465:Cell Movement / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary / Q000235:genetics; D005679:G(M3) Ganglioside / Q000096:biosynthesis / Q000502:physiology*; D005690:Galactose / Q000494:pharmacology; D006031:Glycosylation; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D011518:Proto-Oncogene Proteins; D060245:Tetraspanin 29; D014162:Transfection; D014534:UDPglucose 4-Epimerase / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D015703:Antigens, CD; C554869:CD9 protein, human; D018076:DNA, Complementary; D005679:G(M3) Ganglioside; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D060245:Tetraspanin 29; D014534:UDPglucose 4-Epimerase; C020551:galactose epimerase; D005690:Galactose