N-acetylglucosaminyltransferase IVa regulates metastatic potential of mouse hepatocarcinoma cells through glycosylation of CD147.
N-acetylglucosaminyltransferase (GnT)-IV a is a key enzyme that catalyzes the formation of the GlcNAC β1-4 branch on the core structure of complex N-Glycans, which is the common substrate for other N-acetylglucosaminyltransferases, such as GnT-III and GnT-V. Our recent study indicates that the expression of GnT-IVa in Hca-F cells was much higher than that in Hepa1-6 cells, these two mouse hepatocarcinoma cell lines have high and no metastatic potential in lymph nodes respectively. To investigate the effects of GnT-IVa on the metastasis of hepatocarcinoma, exogenous GnT-IVa was introduced into Hepa1-6 cells, and on the other hand, the expression of GnT-IVa was down-regulated in Hca-F cells. The engineered overexpression of GnT-IVa in Hepa1-6 cells increased the antennary branches of complex N-glycans and reduced bisecting branches in vitro and in vivo, which leads to the increase in migration and metastatic capability of hepatocarcinoma cells. Conversely, down-regulated expression of GnT-IVa in Hca-F cells showed reduced tetra-antennary branches of N-Glycans, and significantly decreased the migration and metastatic capability. Furthermore, we found that the regulated GnT-IVa converts the heterogeneous N-glycosylated forms of CD147 in Hepa1-6 and Hca-F cells, and significantly changed the antennary oligosaccharide structures on CD147. These results suggest that GnT-IVa could be acting as a key role in migration and metastasis of mouse hepatocarcinoma cells through altering the glycosylation of CD147. These findings should be valuable in delineating the important function of GnT-IVa during the process of hepatocarcinoma growth and metastasis.
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Dalian, China.
Jianhui
J
Fan
Shujing
S
Wang
Shengjin
S
Yu
Jingna
J
He
Weilong
W
Zheng
Jianing
J
Zhang
D000818:Animals; D051926:Basigin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002236:Carbohydrate Conformation; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids; D011134:Polysaccharides / Q000737:chemistry; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
D007527:Isoenzymes; D011134:Polysaccharides; D051926:Basigin; D017351:N-Acetylglucosaminyltransferases; C038111:alpha-1,3-mannosylglycoprotein beta-1,4-N-acetylglucosaminyltransferase