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Title 

Overexpression and β-1,6-N-Acetylglucosaminylation-initiated aberrant glycosylation of TIMP-1: A "double whammy" strategy in colon cancer progression

Authors 

Yong Sam KimY H AhnKyoung Jin SongJeong Gu KangJu Hee SongS K JeonHyoung-Chin KimJ S YooJeong Heon Ko

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2012

Citation 

Journal of Biological Chemistry, vol. 287, no. 39, pp. 32467-32478

Abstract 

There has been ongoing debate over whether tissue inhibitor of metalloproteinase-1 (TIMP-1) is pro- or anti-oncogenic. We confirmed that TIMP-1 reinforced cell proliferation in an αvβ3 integrin-dependent manner and conferred resistance against cytotoxicity triggered by TNF-α and IL-2 in WiDr colon cancer cells. The cell-proliferative effects of TIMP-1 contributed to clonogenicity and tumor growth during the onset and early phase of tumor formation in vivo and in vitro. However, mass-produced TIMP-1 impeded further tumor growth by tightly inhibiting the activities of collagenases, which are critical for tumor growth and malignant transformation. Tumor cells could overcome this impasse by overexpression of N-acetylglucosaminyltransferase V, which deteriorates TIMP-1 into an aberrant glycoform. The aberrant glycoform of TIMP-1 was responsible for the mitigated inhibition of collagenases. The outbalanced activities of collagenases can degrade the basement membrane and the interstitial matrix, which act as a physical barrier for tumor growth and progression more efficiently. The concomitant overexpression of TIMP-1 and N-acetylglucosaminyltransferase V enabled WiDr cells to show a higher tumor growth rate as well as more malignant behaviors in a three-dimensional culture system.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M112.370064

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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