Beta1,4-galactosyltransferase V A growth regulator in glioma.

One of the most prominent transformation-associated changes in the sugar chains of glycoproteins is an increase in the large N-glycans of cell surface glycoprotein. beta1,4-galactosyltransferase V (beta1,4GalT V) could effectively galactosylate the GlcNAcbeta1-->6 branch which is a marker of glioma. The expression of beta1,4GalT V is increased in the process of glioma development. beta1,4GalT V regulates the invasion, growth in vivo and in vitro of glioma cells. Downregulation of beta1,4GalT V expression increases the sensitivity of malignant glioma cells to DNA damage drugs. Furthermore, beta1,4GalT V regulates Ras and AKT signaling involving in glioma behaviors. Meanwhile, Ras/MAPK and PI3K/AKT signaling pathways are involved in the transcription regulation of beta1,4GalT V gene. E1AF transcription factor, a downstream target of Ras/MAPK and PI3K/AKT signaling pathways, regulates the transcription of beta1,4GalT V in cooperation with Sp1 transcription factor. The contribution of beta1,4GalT V in glioma development is further confirmed in glioma-initiation cells. beta1,4GalT V regulates the self-renewal of glioma-initiation cells. We now present evidence that beta1,4GalT V functions as a positive growth regulator in glioma and might represent a novel target in glioma therapy.