Int. J. Dev. Biol. 55: 835 - 840 (2011)
doi: 10.1387/ijdb.113336ld
© UPV/EHU Press

The role of non-muscle myosin IIA in aggregation and invasion of human MCF-7 breast cancer cells

Lara Derycke1, Christophe Stove2, Anne-Sophie Vercoutter-Edouart3, Olivier De Wever1, Laurent Dollé1,5, Nathalie Colpaert1, Herman Depypere4, Jean-Claude Michalski3 and Marc Bracke*,1

1Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium, 2Laboratory of Toxicology, Ghent University, Ghent, Belgium, 3Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS/USTL n<0x00B0>8576, IFR 147, France, 4Department of Uro-Gynaecology, Ghent University, Ghent, Belgium, 5Stem Cell Biology Department of Cell Biology (LIVR) Vrije Universiteit Brussel, Brussels, Belgium

ABSTRACT Human MCF-7/6 breast cancer cells differ from their MCF-7/AZ counterparts by their invasiveness in a number of assays in vitro, such as invasion of MCF-7 spheroids into embryonic chick heart fragments or type I collagen gels. Comparative proteomic analysis of these two variants revealed an identical pattern, except for a 230 kDa protein present in the invasive MCF-7/6 variant, but hardly detectable in the non-invasive MCF-7/AZ one. This protein appeared to be the non-muscle myosin IIA heavy chain (NMIIA), also coined MYH9. Experimental inhibition of NMIIA by reducing either its expression (via stable shRNA transduction) or its function (via the specific ATPase inhibitor blebbistatin) underpinned the decisive role of NMIIA in MCF-7 cell invasion. Inhibition of NMIIA indeed blocked the invasion of MCF-7/6 cells in three-dimensional invasion substrata such as embryonic chick heart fragments and type I collagen gels. Invasiveness of MCF-7/6 cells has been related to poor formation and compaction of aggregates, due to a functionally defective E-cadherin/catenin complex. Both genetic and pharmacological inhibition of NMIIA stimulated MCF-7/6 cell aggregation. Together, these data indicate that NMIIA is a decisive protein for MCF-7 cells to invade, indicating that this molecule is a candidate for targeted anti-invasive treatment.


non-muscle myosin, MYH9, invasion, aggregation, MCF-7, breast cancer

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