Open AccessStable expression of α1‐antitrypsin Portland in MDA‐MB‐231 cells increased MT1‐MMP and MMP‐9 levels, but reduced tumour progression.
Author(s) -
Willson J. A.,
Muir C. A.,
Evered C. L.,
Cepeda M. A.,
Damjanovski S.
Publication year - 2018
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-017-0407-5
Subject(s) - matrix metalloproteinase , furin , extracellular matrix , microbiology and biotechnology , in vivo , cell , secretion , chemistry , golgi apparatus , biology , biochemistry , enzyme
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 α1‐antitrypsin Portland (α1‐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‐κB transcription. In vitro analysis showed that α1‐PDX decreased cell protrusions and migration, and this manifested as decreased tumourigenesis when examined in vivo using a chick CAM assay.