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.

Abstract

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.

• Authors: Yong-Sam Kim, Soo Young Hwang, Hye-Yeon Kang, Hosung Sohn, Sejeong Oh, Jin-Young Kim, Jong Shin Yoo, Young Hwan Kim, Cheorl-Ho Kim, Jae-Heung Jeon, Jung Mi Lee, Hyun Ah Kang, Eiji Miyoshi, Naoyuki Taniguchi, Hyang-Sook Yoo, Jeong-Heon Ko
• Journal: Molecular & cellular proteomics : MCP (Mol Cell Proteomics) Vol. 7 Issue 1 Pg. 1-14 (Jan 2008) ISSN: 1535-9476 [Print] United States
• PMID: 17878270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Mutant Proteins
• Neoplasm Proteins
• Tissue Inhibitor of Metalloproteinase-1
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
• Gelatinases

Topics

• Cell Movement (drug effects)
• Colonic Neoplasms (enzymology, pathology)
• Disease Progression
• Electrophoresis, Gel, Two-Dimensional
• Enzyme Inhibitors (pharmacology)
• Gelatinases (antagonists & inhibitors)
• Glycosylation (drug effects)
• HT29 Cells
• Humans
• Kinetics
• Mass Spectrometry
• Mutant Proteins (metabolism)
• N-Acetylglucosaminyltransferases (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Proteins (chemistry, metabolism)
• Protein Binding (drug effects)
• Proteomics (methods)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Transfection