KCS

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 glycomic approach, we identified 36 proteins including tissue inhibitor of metalloproteinase-1 (TIMP-1) as a target protein for GnT-V. TIMP-1 is aberrantly glycosylated as characterized by addition of β1,6-N-acetylglucosamine, polylactosaminylation, and possibly sialylation in GnT-V-overexpressing WiDr cells. The aberrant glycosylation of TIMP-1 is responsible for the mitigated inhibition on both MMP-2 and MMP-9, and this aberrancy is 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 clinical outcome of colon cancer patients. We also selected protein tyrosine phosphatase kappa (PTPk) as a model protein to validate this approach to the discovery of novel biomarkers in colon cancer. PTPk underwent an aberrant glycosylation in GnT-V-overexpressing WiDr cells, and the aberrantly glycosylated PTPk was vulnerable to proteolytic cleavage. The enhanced cleavage of PTPk in GnT-V-overexpressing cells was responsible for the mitigation of the homophilic binding capacity,resulting in an increase in cancer cell migration.