INHIBITION OF MEMBRANE RUFFLING AND EZRIN TRANSLOCATION BY GAMMA-LINOLENIC ACID

Membrane ruffling of a tumour cell is correlated with its motile and m etastatic behaviour. This study examined the effect of gamma linolenic acid (GLA), an anti-cancer agent, on HGF/SF induced membrane ruffling in the human cancer cell line, HT115. HGF induced a rapid appearance of membrane ruffling which was related to increased motility and the t yrosine phosphorylation and translocation of ezrin, a membrane-cytoske leton linker protein. The presence of GLA significantly inhibited both the membrane ruffling and cell motility of the tumour cells, at sub-t oxic concentrations. Western blotting revealed that the tyrosine phosp horylation of ezrin was inhibited by GLA. The translocation ezrin from cytosol and generalised areas of cell membrane to ruffled areas of th e membrane induced by HGF/SF was also inhibited as shown by both indir ect immunofluorescence and transmission electron microscopy. It is con cluded that GLA inhibits HGF/SF induced membrane ruffling via its effe ct on ezrin, and this provides a further molecular explanation for the anti-tumour action of GLA.