Submitted on February 27, 2007
Revised on September 12, 2007
Accepted on September 18, 2007
Functional proteomic study reveals that N-acetylglucosaminyltransferase V reinforces the invasive/metastatic potential of colon cancer through aberrant glycosylation on TIMP-1
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
KRIBB, Daejeon
Corresponding Author: jhko{at}kribb.re.kr
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 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 ß1,6-N-acetylglucosamine, polylactosaminylation, and sialylation in GnT-V-overexpressing WiDr cells. Compared to 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.
