Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells.

Galactosylcerebroside is known to be overexpressed upon the cellular surface of a variety of cancers. In squamous cell carcinomas of the head and neck, one explanation for galactosylcerebroside accumulation has been identified as a transcriptional repression of the galactocerebrosidase gene. Galactocerebrosidase is the enzyme responsible for degrading galactosylcerebroside to ceramide. Ceramide is an important apoptosis activator, whereas galactosylcerebroside functions as an inhibitor. A shift of the ceramide metabolism balance in favor of glycosylated forms has been identified as a mechanism of drug resistance for several antineoplastic agents. Our review elaborates on possible explanations for galactocerebrosidase suppression and on other explanations for increased glycosphingolipid concentration within cancer cell membranes. Furthermore, conjecturable influences of a repressed galactocerebrosidase expression on tumor biology are to be explained. The inhibiting transcription factors YY1 and AP2 have been identified as potential galactocerebrosidase gene suppressors. The resulting accumulation of galactosylcerebroside promotes a reduction of cellular adhesion and inhibits apoptosis, leading to increased cellular growth, migration and prolonged cell survival contributing to carcinogenesis. (c) 2005 Wiley-Liss, Inc.