Title |
Suppression of Cancer Progression by MGAT1 shRNA Knockdown
|
---|---|
Published in |
PLOS ONE, September 2012
|
DOI | 10.1371/journal.pone.0043721 |
Pubmed ID | |
Authors |
Reza Beheshti Zavareh, Mahadeo A. Sukhai, Rose Hurren, Marcela Gronda, Xiaoming Wang, Craig D. Simpson, Neil Maclean, Francis Zih, Troy Ketela, Carol J. Swallow, Jason Moffat, David R. Rose, Harry Schachter, Aaron D. Schimmer, James W. Dennis |
Abstract |
Oncogenic signaling promotes tumor invasion and metastasis, in part, by increasing the expression of tri- and tetra- branched N-glycans. The branched N-glycans bind to galectins forming a multivalent lattice that enhances cell surface residency of growth factor receptors, and focal adhesion turnover. N-acetylglucosaminyltransferase I (MGAT1), the first branching enzyme in the pathway, is required for the addition of all subsequent branches. Here we have introduced MGAT1 shRNA into human HeLa cervical and PC-3-Yellow prostate tumor cells lines, generating cell lines with reduced transcript, enzyme activity and branched N-glycans at the cell surface. MGAT1 knockdown inhibited HeLa cell migration and invasion, but did not alter cell proliferation rates. Swainsonine, an inhibitor of α-mannosidase II immediately downstream of MGAT1, also inhibited cell invasion and was not additive with MGAT1 shRNA, consistent with a common mechanism of action. Focal adhesion and microfilament organization in MGAT1 knockdown cells also indicate a less motile phenotype. In vivo, MGAT1 knockdown in the PC-3-Yellow orthotopic prostate cancer xenograft model significantly decreased primary tumor growth and the incidence of lung metastases. Our results demonstrate that blocking MGAT1 is a potential target for anti-cancer therapy. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Mexico | 1 | 3% |
United States | 1 | 3% |
Unknown | 36 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 10 | 26% |
Researcher | 5 | 13% |
Student > Doctoral Student | 4 | 11% |
Student > Ph. D. Student | 4 | 11% |
Professor > Associate Professor | 3 | 8% |
Other | 7 | 18% |
Unknown | 5 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 13 | 34% |
Biochemistry, Genetics and Molecular Biology | 11 | 29% |
Medicine and Dentistry | 4 | 11% |
Chemistry | 2 | 5% |
Computer Science | 1 | 3% |
Other | 0 | 0% |
Unknown | 7 | 18% |