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Molecular and Cellular Biology, May 2008, p. 2980-2995, Vol. 28, No. 9
0270-7306/08/$08.00+0     doi:10.1128/MCB.02238-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

LRP-1 Silencing Prevents Malignant Cell Invasion despite Increased Pericellular Proteolytic Activities{triangledown}

Stéphane Dedieu,1,{dagger}* Benoît Langlois,1,{dagger} Jérôme Devy,1 Brice Sid,1 Patrick Henriet,2 Hervé Sartelet,1 Georges Bellon,1 Hervé Emonard,1,{ddagger} and Laurent Martiny1,{ddagger}

Université de Reims Champagne-Ardenne, Laboratoire SiRMA, CNRS UMR MEOyC 6237, Moulin de la Housse, Reims, France,1 Cell Biology Unit, de Duve Institute and Université Catholique de Louvain, Brussels, Belgium2

Received 18 December 2007/ Accepted 20 February 2008

The scavenger receptor low-density lipoprotein receptor-related protein 1 (LRP-1) mediates the clearance of a variety of biological molecules from the pericellular environment, including proteinases which degrade the extracellular matrix in cancer progression. However, its accurate functions remain poorly explored and highly controversial. Here we show that LRP-1 silencing by RNA interference results in a drastic inhibition of cell invasion despite a strong stimulation of pericellular matrix metalloproteinase 2 and urokinase-type plasminogen activator proteolytic activities. Cell migration in both two and three dimensions is decreased by LRP-1 silencing. LRP-1-silenced carcinoma cells, which are characterized by major cytoskeleton rearrangements, display atypical overspread morphology with a lack of membrane extensions. LRP-1 silencing accelerates cell attachment, inhibits cell-substrate deadhesion, and induces the accumulation, at the cell periphery, of abundant talin-containing focal adhesion complexes deprived of FAK and paxillin. We conclude that in addition to its role in ligand binding and endocytosis, LRP-1 regulates cytoskeletal organization and adhesive complex turnover in malignant cells by modulating the focal complex composition, thereby promoting invasion.

* Corresponding author. Mailing address: CNRS UMR MEOyC 6237, Laboratoire SiRMA (Signalisation des Récepteurs Matriciels), Université de Reims Champagne-Ardenne, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2, France. Phone: (33) 326 91 32 69. Fax: (33) 326 91 83 66. E-mail: stephane.dedieu{at}univ-reims.fr

{triangledown} Published ahead of print on 3 March 2008.

{dagger} S.D. and B.L. contributed equally to this work.

{ddagger} H.E. and L.M. contributed equally to the supervision of the work.

Molecular and Cellular Biology, May 2008, p. 2980-2995, Vol. 28, No. 9
0270-7306/08/$08.00+0     doi:10.1128/MCB.02238-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Song, H., Li, Y., Lee, J., Schwartz, A. L., Bu, G. (2009). Low-Density Lipoprotein Receptor-Related Protein 1 Promotes Cancer Cell Migration and Invasion by Inducing the Expression of Matrix Metalloproteinases 2 and 9. Cancer Res. 69: 879-886 [Abstract] [Full Text]  


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