Co-ordinated Functions of WASH and Exocyst Complex Underlie the Biogenesis of Invadopodia in Metastatic Breast Tumor Cells

Monteiro, P., Hertzog, M., Rossé, C., Desnos, C., Zech, T., Formstecher, E., Darchen, F., Machesky, L. , Gautreau, A. and Chavrier, P. (2012) Co-ordinated Functions of WASH and Exocyst Complex Underlie the Biogenesis of Invadopodia in Metastatic Breast Tumor Cells. 2012 American Society for Cell Biology Annual Meeting, San Francisco, CA, USA, 15-19 Dec 2012. p. 2077. (doi: 10.1091/mbc.e12-10-0757)

Abstract

The trade-mark of a metastatic tumor cell is its ability to disseminate from the primary tumor by degrading the extracellular matrix and basement membranes that form a barrier around the tissue. Remodelling of the extracellular matrix by metastatic cells requires formation of actinbased protrusions of the plasma membrane called invadopodia, where the trans-membrane matrix metalloproteinase MT1-MMP accumulates. How the cell coordinates targeting of MT1- MMP with actin assembly to form a functional invadopodium remains unclear. Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator WASH on MT1-MMP-containing late endosomes in MDA-MB-231 human breast adenocarcinoma cells. Exocyst and WASH regulate actin assembly on MT1-MMP-containing endosomes to control their dynamics. Both protein complexes are required for invadopodia formation and matrix degradation by a mechanism that involves transient tubular connections between the endosomes and the plasma membrane, which ensure focal delivery of MT1-MMP. These connections are accompanied by recruitment of another Arp2/3 activator, N-WASP, to mature invadopodia and loss of WASH. These findings imply a new definition of invadopodia as structures where late endosomes fuse transiently with the plasma membrane to promote actin assembly and deliver the matrix metalloproteinase to focal sites of matrix degradation.

• Item Type: Conference or Workshop Item
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Machesky, Professor Laura
• Authors: Monteiro, P., Hertzog, M., Rossé, C., Desnos, C., Zech, T., Formstecher, E., Darchen, F., Machesky, L., Gautreau, A., and Chavrier, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• ISSN: 1939-4586