title: The role of non-muscle myosin IIA in aggregation and invasion of human MCF-7 breast cancer cells.
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.
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium.
authors.forename: Lara
authors.initials: L
authors.lastname: Derycke
authors.forename: Christophe
authors.initials: C
authors.lastname: Stove
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Vercoutter-Edouart
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.forename: Laurent
authors.initials: L
authors.lastname: Dollé
authors.forename: Nathalie
authors.initials: N
authors.lastname: Colpaert
authors.forename: Herman
authors.initials: H
authors.lastname: Depypere
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D002449:Cell Aggregation / Q000502:physiology*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D005260:Female; D055785:Gene Knockdown Techniques; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D020409:Molecular Motor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000235:genetics; D018874:Spheroids, Cellular / Q000473:pathology / Q000502:physiology; D014410:Tumor Stem Cell Assay
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D034741:RNA, Small Interfering; C472645:blebbistatin; D018995:Myosin Heavy Chains