期刊
JOURNAL OF CELL COMMUNICATION AND SIGNALING
卷 12, 期 2, 页码 479-488出版社
SPRINGER
DOI: 10.1007/s12079-017-0407-5
关键词
alpha 1-antitrypsin Portland; MDA-MB-231; MMP-9; MT1-MMP; Tumour progression
类别
资金
- Natural Sciences and Engineering Research Council of Canada Discovery Grant
The membrane bound matrix metalloproteinase MT1-MMP plays roles in modulating cell movement, independent of its abilities to remodel the extracellular matrix. Unlike many MMPs, MT1-MMP is activated in the Golgi prior to secretion by a pro-protein convertase, primarily furin. Regulation of the activation of pro-MT1-MMP has been methodically investigated, as altering the level of the active protein has broad implications in both activating other pro-MMPs, including pro-MMP-2, and many subsequent remodelling events. Our previous work in MCF-7 cells has demonstrated that modest, and not extremely high, levels of active MT1-MMP manifests into altered cell morphology and movement. At this low but optimal amount of MT1-MMP protein, changes to MT1-MMP levels are always mirrored by MMP-9 and pERK levels, and always opposite to MMP-2 levels. In this study, stable expression of the furin inhibitor alpha 1-antitrypsin Portland (alpha 1-PDX) in MDA-MB-231 cells increased overall MT1-MMP levels, but cells maintained a 21% proportion of pro-MT1-MMP. The increase in MT1-MMP was mirrored by increases in MMP-9 and pERK, but a decrease in MMP-2. These changes were associated with increased NF-kappa B transcription. In vitro analysis showed that alpha 1-PDX decreased cell protrusions and migration, and this manifested as decreased tumourigenesis when examined in vivo using a chick CAM assay.
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