Academic Journal
Suppression of cancer progression by MGAT1 shRNA knockdown.
| العنوان: | Suppression of cancer progression by MGAT1 shRNA knockdown. |
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| المؤلفون: | 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 |
| المصدر: | PLoS ONE, Vol 7, Iss 9, p e43721 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC3434202?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0043721 |
| URL الوصول: | https://doaj.org/article/76ee1fcc2d2a4fbda66813266fae872d |
| رقم الانضمام: | edsdoj.76ee1fcc2d2a4fbda66813266fae872d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0043721 |