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Molecular & Cellular Proteomics 7:1-14, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

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,*,S

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 and Jeong-Heon Ko^,¶¶

From the Daejeon-KRIBB-Fred Hutchinson Cancer Research Center Research Cooperation Center, ^** Plant Genome Research Center, Protein Therapeutics Research Center, KRIBB, Daejeon 305-806, Korea, Department of Surgery, College of Medicine, Catholic University of Korea, Inchon 403-720, Korea, ^¶ Analysis & Measurement Division, Korea Basic Science Institute, P. O. Box 41, Yusong, Daejeon, 305-333, Korea, ^|| Department of Biological Sciences, Sungkyunkwan University, Suwon City, Kyunggi-Do 440-746, Korea, and the Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine, Suita, Osaka 565-0871, Japan

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 β1,6-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.

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