IntroductionSnail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasion. The Plasminogen Activation system (PA system), including urokinase plasminogen activator (uPA), its receptor, and its inhibitor, plasminogen activator inhibitor type 1(PAI-1), also plays a key role in cancer invasion and metastasis, either through proteolytic degradation or by non proteolytic modulation of cell adhesion and migration. Thus, Snail and the PA system both are over-expressed in cancer and influence this process. In this study we aimed to determine first whether SNAI1 (member of the Snail family) activity is correlated with expression of the PA system components and second, how this correlation can influence tumoral cell migration. Methods: We compared the invasive breast cancer cell-line MDA-MB-231 expressing SNAI1 (MDA-mock) with its derived clone expressing a Dominant Negative form of SNAI1 (SNAI1-DN). Expression of PA system mRNAs was analyzed by cDNA microarrays and real time quantitative reverse transcription – polymerase chain reaction (RT-PCR). Wound healing assays were used to determine cell migration. PAI-1 distribution was assessed by immunostaining. Results: We demonstrated by both cDNA microarrays and real time quantitative RT-PCR that the functional blockade of SNAI1 induces a significant decrease of PAI-1 and uPA transcripts. After performing an in vitro wound-healing assay, we observed that SNAI1-DN cells migrate more slowly than MDA-mock cells and in a more collective manner
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PAI 1 and functional blockade of SNAI1 in breast cancer cells migration
