N-Acetylglucosaminyltransferase V triggers overexpression of MT1-MMP and reinforces the invasive/metastatic potential of cancer cells.
N-Acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes the formation of a β1,6-N-acetylglucosamine (GlcNAc) side chain to a core mannosyl residue in N-linked glycoproteins. Besides its direct function of producing aberrant glycoproteins, it promotes cancer progression by its involvement in the stimulation of oncoproteins. Herein, we report that GnT-V guided the transcriptional activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) in cancer cells. The activated MT1-MMP expression had dual effects on cancer progression. It not only promoted proteolytic activity for cancer cells per se, but also led to the activation of MMP-2. Consequently, the activation of the two MMPs triggered by GnT-V intensified the invasive potential. A quantitative analysis using clinical tissues revealed a relatively strong correlation between GnT-V overexpression and MT1-MMP upregulation. In this study, we report for the first time that GnT-V directs cancer progression by modulating MMPs in cancer.
Cancer Biomarkers Development Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, South Korea.
Ju Hee
JH
Lee
Jeong Gu
JG
Kang
Kyoung Jin
KJ
Song
Seong Kook
SK
Jeon
Sejeong
S
Oh
Yong-Sam
YS
Kim
Jeong-Heon
JH
Ko
D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14