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In the present study, we investigated invasiveness, migration, matrix metalloproteinases (MMPs) activity, and cell survival of MDA\u2010MB\u2010231 cells under normoxia, hypoxia, and hypoxia\/reoxygenation (H\/R). Moreover, to assess the importance of hypoxia and autophagy on the parameters studied, cells were either left untreated or treated with Chetomin (a selective inhibitor of HIF\u20101\u03b1) or trifluoperazine (TFP, an activator of autophagy). We found that hypoxia and H\/R stimulated invasiveness and migration of MDA\u2010MB\u2010231 cells with an increased MMP\u20102 activity. Chetomin and TFP differently regulated the cellular behavior under the oxygenation conditions studied. In fact, Chetomin was most effective in inhibiting cell invasion, MMPs activity, and cell survival under hypoxia but not normoxia or H\/R. By contrast, TFP inhibition of cell invasion, migration, and cell survival was independent from oxygenation conditions. TFP\u2010induced autophagy was inhibited by light chain protein 3 (LC3) silencing or 3\u2010methyladenine (3MA) treatment. In fact, LC3\u2010silenced cells were able to invade in the presence of TFP without any GATE16 processing and p62 degradation. Immunofluorescence assay showed that LC3 silencing inhibited TFP\u2010induced autophagosome formation. However, we also showed that both TPF treatment and LC3 silencing caused cytoskeleton impairments suggesting a possible interaction between LC3 and cytoskeleton components. In conclusion, our study shows that hypoxia and autophagy by acting on common (HIF\u20101\u03b1) or separate (MMPs, cytoskeleton) targets differently regulate cell invasion, MMPs activity, and survival. J. Cell. Physiol. 223: 359\u2013368, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22041","type":"journal-article","created":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T17:32:48Z","timestamp":1264699968000},"page":"359-368","source":"Crossref","is-referenced-by-count":59,"title":["Role of hypoxia and autophagy in MDA\u2010MB\u2010231 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