English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/9390
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

PAI-1 and functional blockade of SNAI1 in breast cancer cell migration

AuthorsFabre-Guillevin, Elizabeth; Peinado, Héctor; Moreno-Bueno, Gema ; Palacios, José; Cano, Amparo ; Barlovatz-Meimon, Georgia
KeywordsBreast cancer
Tumoral cell migration
Plasminogen Activation (PA) system
Snail family
SNAI1
Transcriptional repressors
Epithelial-mesenchymal transition (EMT)
Issue Date3-Dec-2008
PublisherBioMed Central
CitationBreast Cancer Research 10: R100 (2008)
Abstract[Introduction]: Snail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasion. The Plasminogen Activation (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 are both over-expressed in cancer and influence this process. In this study we aimed to determine if the activity of SNAI1 (a member of the Snail family) is correlated with expression of the PA system components and how this correlation can influence tumoural 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 analysed by cDNA microarrays and real-time quantitative 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 realtime 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. The blockade of SNAI1 activity resulted in the redistribution of PAI-1 in SNAI1-DN cells decorating large lamellipodia, which are commonly found structures in these cells.
[Conclusions]: In the absence of functional SNAI1, the expression of PAI-1 transcripts is decreased, although the protein is redistributed at the leading edge of migrating cells in a manner comparable with that seen in normal epithelial cells.
Description12 pages, 5 figures.-- PMID: 19055748 [PubMed].-- et al.
Publisher version (URL)http://dx.doi.org/10.1186/bcr2203
URIhttp://hdl.handle.net/10261/9390
DOI10.1186/bcr2203
ISSN1465-5411
Appears in Collections:(IIBB) Artículos
(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
PAI1_functional_blockade.pdfMain text2,27 MBAdobe PDFThumbnail
View/Open
PAI1_functional_blockade_S1.docSupplementary data file122,5 kBMicrosoft WordView/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.