Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Sakurai-Yageta, M. Articles by Chavrier, P. PubMed PubMed Citation Articles by Sakurai-Yageta, M. Articles by Chavrier, P. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Substance via MeSH Medline Plus Health Information Breast Cancer Related Collections Related In this Issue article Social Bookmarking                      What's this?

¹ Institut Curie, Centre de Recherche, Paris F-75248, France
² Centre National de la Recherche Scientifique, Unite Mixte Recherche 144, Paris F-75248, France
³ Hybrigenics SA, Paris F-75014, France
⁴ Institut National de la Santé et de la Recherche Médicale, Unite 528, Paris F-75248, France
⁵ Department of Biological Sciences and ⁶ Walther Cancer Research Center, University of Notre Dame, Notre Dame, IN 46556

Correspondence to Philippe Chavrier: philippe.chavrier{at}curie.fr

Invadopodia are actin-based membrane protrusions formed at contact sites between invasive tumor cells and the extracellular matrix with matrix proteolytic activity. Actin regulatory proteins participate in invadopodia formation, whereas matrix degradation requires metalloproteinases (MMPs) targeted to invadopodia. In this study, we show that the vesicle-tethering exocyst complex is required for matrix proteolysis and invasion of breast carcinoma cells. We demonstrate that the exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA, which are essential for matrix degradation. Interaction between IQGAP1 and the exocyst is necessary for invadopodia activity because enhancement of matrix degradation induced by the expression of IQGAP1 is lost upon deletion of the exocyst-binding site. We further show that the exocyst and IQGAP1 are required for the accumulation of cell surface membrane type 1 MMP at invadopodia. Based on these results, we propose that invadopodia function in tumor cells relies on the coordination of cytoskeletal assembly and exocytosis downstream of Rho guanosine triphosphatases.

M. Sakurai-Yageta and C. Recchi contributed equally to this paper.

M. Sakurai-Yageta's present address is Division of Molecular Pathology, Dept. of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.

C. Recchi's present address is Molecular and Cellular Medicine, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.

Abbreviations used in this paper: F-actin, filamentous actin; MMP, metalloproteinase; MT, membrane type; WT, wild type.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related In this Issue article

Partner up to invade

Richard Robinson
J. Cell Biol. 2008 181: 875. [Full Text] [PDF]

This article has been cited by other articles:

• Robinson, R. (2008). Partner up to invade. J. Cell Biol. 181: 875-875 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents