Cheorl-Ho Kim
SungKyunKwan University, Korea
Title: Cellular roles of ganglioside GM3 biosynthesis in human cancer cells
Biography
Biography: Cheorl-Ho Kim
Abstract
Ganglioside GM3, sialic acid (NeuAc)-containing glycosphingolipid, is the first and the simplest of the gangliosides and are found on the outer leaflet of the plasma membrane in vertebrates. It plays important roles in a large variety of biological processes, such as cellular interactions, differentiation, oncogenesis, adhesion, cell growth, and receptor function in various cell systems. Ganglioside GM3 is synthesized by lactosylceramide α-2,3-sialyltransferase (hST3Gal V, EC 2.4.99.9) which catalyzes the transfer of NeuAc from CMP-NeuAc to the non-reducing terminal galactose of lactosylceramide in human. The amount of ganglioside GM3 increases with a concomitant increase of hST3Gal V activity during megakaryocytic differentiation of K562 cells treated with PMA that is a megakaryocytic differentiation inducer, but not with an erythrocyte differentiation inducer, hemin. Ganglioside GM3 may play an important role as a trigger in differentiation induction of K562 cells. hST3Gal V is a key regulatory enzyme for ganglioside biosynthesis because it catalyzes the first committed step in the synthesis of nearly all gangliosides. Differentiation of K562 cells requires Erk1/2 activation and p38 MAPK inhibition for the transcriptional activity of lactosylceramide α-2,3-sialyltransferase (hST3Gal V) and synthesis of ganglioside GM3. The expression of hST3Gal V mRNA induces expression of the megakaryocytic markers and differentiation of K562 cells. Ganglioside GM3 mediates megakaryocytic differentiation of human chronic myelogenous cells and apoptosis of many human cancer cells.