This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.02238-07v1 28/9/2980    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Dedieu, S. Articles by Martiny, L. PubMed PubMed Citation Articles by Dedieu, S. Articles by Martiny, L.

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

Stéphane Dedieu,^1,* Benoît Langlois,^1, Jérôme Devy,¹ Brice Sid,¹ Patrick Henriet,² Hervé Sartelet,¹ Georges Bellon,¹ Hervé Emonard,^1, and Laurent Martiny^1,

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.

Published ahead of print on 3 March 2008.

S.D. and B.L. contributed equally to this work.

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