ALPHA-6-BETA-1-INTEGRIN, A MAJOR CELL-SURFACE CARRIER OF BETA-1-6-BRANCHED OLIGOSACCHARIDES, MEDIATES MIGRATION OF EJ-RAS-TRANSFORMED FIBROBLASTS ON LAMININ-1 INDEPENDENTLY OF ITS GLYCOSYLATION STATE

EJ-ras oncogene-induced malignant transformation is characterized by a series of changes in cell surface carbohydrates and cell-cell and cel l-matrix interactions, Here, we show that EJ-ras-transformed NIH-3T3 f ibroblasts acquired a migratory phenotype on laminin-1 surfaces, Such a phenotype was accompanied by overexpression of: (a) functional alpha 6 beta 1, but not other laminin binding beta 1-integrins; and (b) gly coconjugates on the cell surface bearing large oligosaccharides recogn ized by leukoagglutinin from Phaseolus vulgar is (L-PHA). The internal pool of pre-beta 1-integrins was differently regulated in EJ-ras-tran sformed cells compared with non-transfected fibroblasts. Conversion of pre-beta 1- into mature beta 1-integrins was faster in EJ-ras-transfo rmed cells, a process associated with the overexpression of the alpha 6-chain, Overexpression of L-PHA-reactive oligosaccharides is dependen t on the activity of N-acetylglucosaminyltransferase V, which is incre ased in transformed cells [J. W. Dennis et al., Science (Washington DC ), 236: 582-585, 1987], We show that beta 1-integrins were the major c arriers of L-PHA-reactive oligosaccharides on the cell surface, This g lycosylation pattern, however, was not necessary for either the cell s urface expression of beta 1-integrins or their functional activity in the migratory response to laminin-1, Moreover, EJ-ras-transformed fibr oblasts aggregated spontaneously, These effects were not observed in c -jun-transfected fibroblasts, which were unable to migrate on laminin, did not overexpress either beta 1-integrins or L-PHA-reactive oligosa ccharides, and did not self-aggregate.