Beta1,4-galactosyltransferase V regulates self-renewal of glioma-initiating cell.
Glioma results from unregulated expansion of a self-renewing glioma-initiating cell population. The regulatory pathways which are essential for sustaining the self-renewal of glioma-initiating cells remain largely unknown. Cell surface N-linked oligosaccharides play functional roles in determining cell fate and are associated with glioma malignancy. Previously, we have reported that beta1,4-galactosyltransferase V (beta1,4GalT V) effectively galactosylates the GlcNAcbeta1-->6Man arm of the highly branched N-glycans and positively regulates glioma cell growth. Here, we show that decreasing the expression of beta1,4GalT V by RNA interference in glioma cells attenuated the formation of polylactosamine and inhibited the ability of tumor formation in vivo. Down-regulation of beta1,4GalT V depleted CD133-positive cells in glioma xenograft, and inhibited the self-renewal capacity and the tumorigenic potential of glioma-initiating cells. These data reveal a critical role of beta1,4GalT V in the self-renewal and tumorigenicity of glioma-initiating cells, and indicate that manipulating beta1,4GalT V expression may have therapeutic potential for the treatment of malignant glioma.
Wei
Yuanyan
Y
Key Laboratory of Glycoconjuates Research, Ministry of Public Health & Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
Zhou
Fengbiao
F
Ge
Yuqing
Y
Chen
Hong
H
Cui
Chunhong
C
Li
Qiuping
Q
Liu
Dan
D
Yang
Zhiyuan
Z
Wu
Guoqiang
G
Sun
Shuhui
S
Gu
Jianxin
J
Jiang
Jianhai
J
D000606:Amino Sugars / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D005700:Galactosyltransferases / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000473:pathology*; D011134:Polysaccharides / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000606:Amino Sugars; D011134:Polysaccharides; D034741:RNA, Small Interfering; C066929:polylactosamine; D005700:Galactosyltransferases; C419408:beta-1,4-galactosyltransferase V