title: Mechanical interplay between invadopodia and the nucleus in cultured cancer cells.
abstract: Invadopodia are actin-rich membrane protrusions through which cells adhere to the extracellular matrix and degrade it. In this study, we explored the mechanical interactions of invadopodia in melanoma cells, using a combination of correlative light and electron microscopy. We show here that the core actin bundle of most invadopodia interacts with integrin-containing matrix adhesions at its basal end, extends through a microtubule-rich cytoplasm, and at its apical end, interacts with the nuclear envelope and indents it. Abolishment of invadopodia by microtubules or src inhibitors leads to the disappearance of these nuclear indentations. Based on the indentation profile and the viscoelastic properties of the nucleus, the force applied by invadopodia is estimated to be in the nanoNewton range. We further show that knockdown of the LINC complex components nesprin 2 or SUN1 leads to a substantial increase in the prominence of the adhesion domains at the opposite end of the invadopodia. We discuss this unexpected, long-range mechanical interplay between the apical and basal domains of invadopodia, and its possible involvement in the penetration of invadopodia into the matrix.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Or-Yam
authors.initials: OY
authors.lastname: Revach
authors.affiliation: Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Allon
authors.initials: A
authors.lastname: Weiner
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Katya
authors.initials: K
authors.lastname: Rechav
authors.affiliation: 1] Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel [2] Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Sabanay
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Livne
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Geiger
mesh_terms: D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure*; D000069261:Podosomes / Q000473:pathology / Q000648:ultrastructure*
chemical_list: D000199:Actins
references.citation: Methods Cell Biol. 2010;98:121-41
references.pmid: 20816233
references.citation: Annu Rev Cell Dev Biol. 2011;27:185-211
references.pmid: 21801014
references.citation: Cancer Sci. 2008 Nov;99(11):2252-9
references.pmid: 18795939
references.citation: Oncotarget. 2011 Jul;2(7):562-8
references.pmid: 21725138
references.citation: Cell. 2011 Jun 24;145(7):1012-22
references.pmid: 21703446
references.citation: J Cell Sci. 2013 Jul 15;126(Pt 14):2979-89
references.pmid: 23843616
references.citation: Cancer Res. 2009 Apr 1;69(7):2792-800
references.pmid: 19276357
references.citation: Science. 2014 Aug 29;345(6200):1062-5
references.pmid: 25170155
references.citation: J Cell Sci. 2012 Feb 1;125(Pt 3):724-34
references.pmid: 22389406
references.citation: J Cell Biol. 2009 Aug 24;186(4):571-87
references.pmid: 19704022
references.citation: Eur J Cell Biol. 2008 Sep;87(8-9):491-506
references.pmid: 18417250
references.citation: J R Soc Interface. 2005 Mar 22;2(2):63-9
references.pmid: 16849165
references.citation: Int Rev Cell Mol Biol. 2009;275:1-34
references.pmid: 19491051
references.citation: Science. 2013 Aug 30;341(6149):1240104
references.pmid: 23990565
references.citation: Trends Cell Biol. 2007 Mar;17(3):107-17
references.pmid: 17275303
references.citation: Nat Rev Mol Cell Biol. 2011 Jul;12(7):413-26
references.pmid: 21697900
references.citation: Eur J Cell Biol. 2010 Sep;89(9):674-80
references.pmid: 20537759
references.citation: J Biol Chem. 2008 May 16;283(20):13799-805
references.pmid: 18353776
references.citation: Biochem Biophys Res Commun. 2000 Mar 24;269(3):781-6
references.pmid: 10720492
references.citation: Nat Rev Cancer. 2003 Dec;3(12):921-30
references.pmid: 14737122
references.citation: Cancer Res. 2007 May 1;67(9):4227-35
references.pmid: 17483334
references.citation: J Cell Sci. 2010 Feb 1;123(Pt 3):297-308
references.pmid: 20130138
references.citation: Cell. 2011 Nov 23;147(5):992-1009
references.pmid: 22118458
references.citation: Physiol Rev. 1998 Jul;78(3):763-81
references.pmid: 9674694
references.citation: Microsc Microanal. 2010 Dec;16(6):747-54
references.pmid: 20961484
references.citation: Science. 2012 May 25;336(6084):999-1003
references.pmid: 22499806
references.citation: Nat Rev Mol Cell Biol. 2009 Jan;10(1):75-82
references.pmid: 19197334
references.citation: Acta Biomater. 2014 May;10(5):1886-96
references.pmid: 24412623
references.citation: J Cell Sci. 2009 Sep 1;122(Pt 17):3037-49
references.pmid: 19692590
references.citation: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12962-6
references.pmid: 7809155
references.citation: Eur J Cell Biol. 2006 Dec;85(12):1217-31
references.pmid: 17010475
references.citation: J Cell Biol. 2010 May 3;189(3):541-56
references.pmid: 20421424
references.citation: Nat Rev Cancer. 2011 Mar;11(3):177-87
references.pmid: 21326322
references.citation: Mol Biol Cell. 2003 Mar;14(3):1074-84
references.pmid: 12631724
references.citation: Eur J Cell Biol. 2008 Sep;87(8-9):555-67
references.pmid: 18417249
references.citation: J Cell Biol. 2008 Jul 14;182(1):157-69
references.pmid: 18606851
references.citation: Phys Biol. 2013 Dec;10(6):065002
references.pmid: 24304807
references.citation: Methods Cell Biol. 2001;63:613-27
references.pmid: 11060862
references.citation: Eur J Cell Biol. 2012 Nov-Dec;91(11-12):961-8
references.pmid: 22564726
references.citation: J Biomech. 2002 Feb;35(2):177-87
references.pmid: 11784536
references.citation: Curr Opin Cell Biol. 2008 Apr;20(2):235-41
references.pmid: 18337078
references.citation: Oncogene. 2010 Dec 2;29(48):6402-8
references.pmid: 20956943
references.citation: Methods Mol Biol. 2009;522:211-9
references.pmid: 19247615
references.citation: Trends Cell Biol. 2002 Mar;12(3):112-20
references.pmid: 11859023
references.citation: J Cell Biol. 2011 Nov 28;195(5):903-20
references.pmid: 22105349
references.citation: Cell. 2006 Aug 25;126(4):677-89
references.pmid: 16923388
references.citation: Cell Adh Migr. 2014;8(3):215-25
references.pmid: 24714132
references.citation: J Cell Biol. 2012 Apr 30;197(3):421-37
references.pmid: 22529104
references.citation: Cancer Metastasis Rev. 2009 Jun;28(1-2):137-49
references.pmid: 19153671
references.citation: J Cell Sci. 2005 Jan 1;118(Pt 1):19-26
references.pmid: 15615780
references.citation: Eur J Cell Biol. 2012 Nov-Dec;91(11-12):896-901
references.pmid: 22633185
references.citation: Biochem Soc Trans. 2012 Feb;40(1):129-32
references.pmid: 22260678
references.citation: J Cell Biol. 2005 Jan 31;168(3):441-52
references.pmid: 15684033
references.citation: Biol Open. 2012 Aug 15;1(8):711-22
references.pmid: 23213464
references.citation: ACS Nano. 2014 Apr 22;8(4):3821-8
references.pmid: 24673613
references.citation: FEBS Lett. 2008 Jun 18;582(14):2102-11
references.pmid: 18396168
references.citation: Biomaterials. 2014 Jan;35(3):961-9
references.pmid: 24183171
references.citation: J Cell Sci. 2009 Aug 1;122(Pt 15):2727-40
references.pmid: 19596797
references.citation: J Appl Physiol (1985). 2008 Aug;105(2):652-61
references.pmid: 18535125
references.citation: J Cell Sci. 2011 Feb 1;124(Pt 3):299-310
references.pmid: 21242309