MT1-MMP directs force-producing proteolytic contacts that drive tumor cell invasion

Robin Ferrari (), Gaëlle Martin, Oya Tagit, Alan Guichard, Alessandra Cambi, Raphaël Voituriez, Stéphane Vassilopoulos () and Philippe Chavrier ()
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Robin Ferrari: Sorbonne Université, Institut Curie, PSL Research University, CNRS, UMR 144
Gaëlle Martin: PSL Research University, CNRS, UMR 144
Oya Tagit: Radboud University Medical Center, Nijmegen and Oncode Institute
Alan Guichard: PSL Research University, CNRS, UMR 144
Alessandra Cambi: Radboud University Medical Center
Raphaël Voituriez: Sorbonne Université, CNRS, UMR 8237, Jean Perrin Laboratory
Stéphane Vassilopoulos: Sorbonne Université, INSERM UMRS 974, Institute of Myology
Philippe Chavrier: PSL Research University, CNRS, UMR 144

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Unraveling the mechanisms that govern the formation and function of invadopodia is essential towards the prevention of cancer spread. Here, we characterize the ultrastructural organization, dynamics and mechanical properties of collagenotytic invadopodia forming at the interface between breast cancer cells and a physiologic fibrillary type I collagen matrix. Our study highlights an uncovered role for MT1-MMP in directing invadopodia assembly independent of its proteolytic activity. Electron microscopy analysis reveals a polymerized Arp2/3 actin network at the concave side of the curved invadopodia in association with the collagen fibers. Actin polymerization is shown to produce pushing forces that repel the confining matrix fibers, and requires MT1-MMP matrix-degradative activity to widen the matrix pores and generate the invasive pathway. A theoretical model is proposed whereby pushing forces result from actin assembly and frictional forces in the actin meshwork due to the curved geometry of the matrix fibers that counterbalance resisting forces by the collagen fibers.

Date: 2019
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DOI: 10.1038/s41467-019-12930-y

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