Expression of gangliosides, GD1a, and sialyl paragloboside is regulated by NF-κB-dependent transcriptional control of α2,3-sialyltransferase I, II, and VI in human castration-resistant prostate cancer cells.

Gangliosides are sialic acid-containing glycosphingolipids that are associated with tumor malignancy and progression. Among the enzymes required for the production of gangliosides, sialyltransferases have received much attention in terms of their relationship with cancer. In our previous report, ganglioside GD1a and sialyl paragloboside (SPG), a neolacto-series ganglioside, were much more abundant in PC3 and DU145 cells, castration-resistant prostate cancer cells, as compared with hormone-sensitive prostate cancer cells and normal prostate epithelium. GD1a is synthesized from GM1 by α2,3 sialyltransferase (ST3Gal) I and mainly by ST3Gal II. The enzyme to synthesize SPG is ST3Gal VI. The high production of GD1a and SPG in castration-resistant prostate cancer cells was correlated with the high expression of ST3Gal II and VI, respectively. The expression of ST3Gal I and II was mildly induced by phorbol-12-myristate-13-acetate (PMA), and PMA-induced expression of ST3Gal I and ST3Gal II was inhibited by NF-κB decoy oligodeoxynucleotides (ODN) but not by AP-1 decoy ODN. Among the five mammalian homologs of the NF-κB family, RelB RNAi most effectively inhibited the expression of ST3Gal I and ST3Gal II. The expression of ST3Gal VI was also most effectively inhibited by RelB RNAi. The amount of GD1a and SPG was significantly reduced by RelB siRNA treatment in PC3 cells. Thus, the production of GD1a and SPG in castration-resistant prostate cancer cells was indirectly controlled by NF-κB, mainly by RelB, through the transcriptional regulation of ST3Gal I, II, and VI.