Glycosphingolipids govern gene expression.
To elucidate the biological significance of the lactosylceramide (LacCer) branching in glycosphingolipid (GSL) biosynthesis, we established ganglioside GM3- and lactosylsulfatide SM3-reconstituted cells by introducing the GM3 synthase gene and the sulfotransferase gene, respectively. In SM3-expressing cells, the reduction of beta1 integrin mRNA expression, the reduced adhesivity to fibronectin and laminin, and the suppression of anchorage-independent growth (tumorigenic potential) were observed. On the other hand, in GM3-expressing cells, anchorage-independent growth was promoted and the expression of PDGF alpha receptor mRNA was specifically reduced. Interestingly enough, no change in anchorage-dependent growth was observed in these cells, and tumorigenic signals were controlled selectively in both positive and negative directions. Thus, the spatio-temporal, gene expression control mechanism by individual GSL molecules accumulating in the cell membrane microdomain (raft) has been proven.
Inokuchi
Jin-ichi
J
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan. inokuchi@kinou02.pharm.hokudai.ac.jp
Kabayama
Kazuya
K
Uemura
Satoshi
S
Igarashi
Yasuyuki
Y
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003260:Contact Inhibition; D006224:Cricetinae; D005353:Fibronectins / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000378:metabolism; D005786:Gene Expression Regulation; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D007790:Lactosylceramides / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D005353:Fibronectins; D005679:G(M3) Ganglioside; D006028:Glycosphingolipids; D019012:Integrin beta1; D016023:Integrins; D007790:Lactosylceramides; D007797:Laminin; D012333:RNA, Messenger; C009744:CDw17 antigen; D017479:Receptors, Platelet-Derived Growth Factor