Functional proteomics study reveals that N-Acetylglucosaminyltransferase V reinforces the invasive/metastatic potential of colon cancer through aberrant glycosylation on tissue inhibitor of metalloproteinase-1.
N-Acetylglucosaminyltransferase-V (GnT-V) has been reported to be up-regulated in invasive/metastatic cancer cells, but a comprehensive understanding of how the transferase correlates with the invasive/metastatic potential is not currently available. Through a glycomics approach, we identified 30 proteins, including tissue inhibitor of metalloproteinase-1 (TIMP-1), as a target protein for GnT-V in human colon cancer cell WiDr. TIMP-1 was aberrantly glycosylated as characterized by the addition of beta1,6-N-acetylglucosamine, polylactosaminylation, and sialylation in GnT-V-overexpressing WiDr cells. Compared with normal TIMP-1, the aberrantly glycosylated TIMP-1 showed the weaker inhibition on both matrix metalloproteinase (MMP)-2 and MMP-9, and this aberrancy was closely associated with cancer cell invasion and metastasis in vivo as well as in vitro. Integrated data, both of TIMP-1 expression level and aberrant glycosylation, could provide important information to aid to improve the clinical outcome of colon cancer patients.
Kim
Yong-Sam
YS
Daejeon-KRIBB-Fred Hutchinson Cancer Research Center Research Cooperation Center, Daejeon, Korea.
Hwang
Soo Young
SY
Kang
Hye-Yeon
HY
Sohn
Hosung
H
Oh
Sejeong
S
Kim
Jin-Young
JY
Yoo
Jong Shin
JS
Kim
Young Hwan
YH
Kim
Cheorl-Ho
CH
Jeon
Jae-Heung
JH
Lee
Jung Mi
JM
Kang
Hyun Ah
HA
Miyoshi
Eiji
E
Taniguchi
Naoyuki
N
Yoo
Hyang-Sook
HS
Ko
Jeong-Heon
JH
D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018093:Gelatinases / Q000037:antagonists & inhibitors; D006031:Glycosylation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D050505:Mutant Proteins / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014162:Transfection
D004791:Enzyme Inhibitors; D050505:Mutant Proteins; D009363:Neoplasm Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D018093:Gelatinases