title: Actin machinery and mechanosensitivity in invadopodia, podosomes and focal adhesions.
abstract: The invasiveness of cells is correlated with the presence of dynamic actin-rich membrane structures called invadopodia, which are membrane protrusions that are associated with localized polymerization of sub-membrane actin filaments. Similar to focal adhesions and podosomes, invadopodia are cell-matrix adhesion sites. Indeed, invadopodia share several features with podosomes, but whether they are distinct structures is still a matter of debate. Invadopodia are built upon an N-WASP-dependent branched actin network, and the Rho GTPase Cdc42 is involved in inducing invadopodial-membrane protrusion, which is mediated by actin filaments that are organized in bundles to form an actin core. Actin-core formation is thought to be an early step in invadopodium assembly, and the actin core is perpendicular to the extracellular matrix and the plasma membrane; this contrasts with the tangential orientation of actin stress fibers anchored to focal adhesions. In this Commentary, we attempt to summarize recent insights into the actin dynamics of invadopodia and podosomes, and the forces that are transmitted through these invasive structures. Although the mechanisms underlying force-dependent regulation of invadopodia and podosomes are largely unknown compared with those of focal adhesions, these structures do exhibit mechanosensitivity. Actin dynamics and associated forces might be key elements in discriminating between invadopodia, podosomes and focal adhesions. Targeting actin-regulatory molecules that specifically promote invadopodium formation is an attractive strategy against cancer-cell invasion.
authors.affiliation: INSERM U823 Institut Albert Bonniot, Université Joseph Fourier, CNRS ERL3148, Equipe DySAD, Site Santé, BP 170, Grenoble, France. corinne.albiges-rizo@ujf-grenoble.fr
authors.forename: Corinne
authors.initials: C
authors.lastname: Albiges-Rizo
authors.forename: Olivier
authors.initials: O
authors.lastname: Destaing
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fourcade
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Planus
authors.forename: Marc R
authors.initials: MR
authors.lastname: Block
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D021961:Cell Membrane Structures / Q000737:chemistry* / Q000378:metabolism; D002477:Cells / Q000737:chemistry* / Q000378:metabolism; D022001:Focal Adhesions / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology
references.citation: Exp Cell Res. 2005 Jul 15;307(2):342-53
references.pmid: 15894313
references.citation: Curr Opin Cell Biol. 2009 Feb;21(1):47-50
references.pmid: 19208463
references.citation: J Biol Chem. 2005 Jul 1;280(26):24857-63
references.pmid: 15866871
references.citation: Lancet Oncol. 2005 Oct;6(10):798-808
references.pmid: 16198986
references.citation: Nat Cell Biol. 2004 Oct;6(10):977-83
references.pmid: 15448700
references.citation: Curr Biol. 2006 Feb 7;16(3):242-51
references.pmid: 16461277
references.citation: Biochem Biophys Res Commun. 2004 Nov 26;324(4):1155-64
references.pmid: 15504335
references.citation: EMBO J. 2008 Nov 5;27(21):2817-28
references.pmid: 18923421
references.citation: Int J Cancer. 2004 May 10;109(6):909-18
references.pmid: 15027125
references.citation: J Cell Biol. 2008 Jul 14;182(1):157-69
references.pmid: 18606851
references.citation: Nat Cell Biol. 2008 Sep;10(9):1062-8
references.pmid: 19160486
references.citation: Eur J Cell Biol. 2006 Apr;85(3-4):219-24
references.pmid: 16546564
references.citation: Mol Biol Cell. 2008 Jan;19(1):394-404
references.pmid: 17978100
references.citation: PLoS One. 2007 Jan 31;2(1):e179
references.pmid: 17264882
references.citation: Mol Biol Cell. 2008 Feb;19(2):633-45
references.pmid: 18045996
references.citation: Exp Cell Res. 1985 Jul;159(1):141-57
references.pmid: 2411576
references.citation: J Cell Biol. 2006 May 22;173(4):571-85
references.pmid: 16702231
references.citation: Cancer Res. 2009 Apr 1;69(7):2792-800
references.pmid: 19276357
references.citation: Curr Biol. 1999 Jun 17;9(12):640-8
references.pmid: 10375527
references.citation: J Cell Sci. 2009 Jan 15;122(Pt 2):199-206
references.pmid: 19118212
references.citation: Science. 1996 Jul 12;273(5272):245-8
references.pmid: 8662509
references.citation: J Biol Chem. 2009 Mar 27;284(13):8548-56
references.pmid: 19155218
references.citation: J Biol Chem. 2003 May 9;278(19):16844-51
references.pmid: 12615925
references.citation: J Cell Biol. 2003 Feb 3;160(3):409-21
references.pmid: 12566431
references.citation: J Cell Biol. 2007 Mar 12;176(6):877-88
references.pmid: 17353363
references.citation: Nat Cell Biol. 2007 Sep;9(9):1046-56
references.pmid: 17721515
references.citation: J Cell Biol. 2001 Jan 8;152(1):181-95
references.pmid: 11149930
references.citation: Biophys J. 2009 Mar 4;96(5):2009-22
references.pmid: 19254561
references.citation: Eur J Cell Biol. 2006 Dec;85(12):1217-31
references.pmid: 17010475
references.citation: Annu Rev Biophys Biomol Struct. 2000;29:545-76
references.pmid: 10940259
references.citation: Nat Cell Biol. 1999 Jul;1(3):136-43
references.pmid: 10559899
references.citation: J Cell Biol. 2001 Jun 11;153(6):1175-86
references.pmid: 11402062
references.citation: J Cell Sci. 1998 Apr;111 ( Pt 7):929-40
references.pmid: 9490637
references.citation: J Cell Sci. 1999 Jun;112 ( Pt 11):1655-69
references.pmid: 10318759
references.citation: J Clin Invest. 2007 Oct;117(10):2962-73
references.pmid: 17885682
references.citation: Genes Dev. 2003 Jan 1;17(1):7-30
references.pmid: 12514095
references.citation: Curr Biol. 2005 Jul 26;15(14):1276-85
references.pmid: 16051170
references.citation: Mol Biol Cell. 2005 Sep;16(9):4329-40
references.pmid: 16000373
references.citation: J Cell Biol. 2006 Feb 27;172(5):771-82
references.pmid: 16505170
references.citation: Mol Cell Biol. 1993 Dec;13(12):7892-900
references.pmid: 8247004
references.citation: Cancer Res. 2007 Apr 15;67(8):3505-11
references.pmid: 17440055
references.citation: J Cell Biol. 2005 Oct 24;171(2):209-15
references.pmid: 16247023
references.citation: J Cell Biol. 1996 May;133(4):895-910
references.pmid: 8666673
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1451-6
references.pmid: 19164586
references.citation: Eur J Cell Biol. 2008 Sep;87(8-9):459-68
references.pmid: 18294724
references.citation: J Cell Sci. 2008 Sep 1;121(Pt 17):2795-804
references.pmid: 18682496
references.citation: PLoS Biol. 2007 Oct 2;5(10):e268
references.pmid: 17914904
references.citation: Dev Cell. 2004 Oct;7(4):585-95
references.pmid: 15469846
references.citation: Biophys J. 2008 Dec;95(11):5424-31
references.pmid: 18689459
references.citation: Mol Biol Cell. 1999 Apr;10(4):935-45
references.pmid: 10198048
references.citation: J Biol Chem. 2008 Apr 11;283(15):9814-9
references.pmid: 18283104
references.citation: J Biol Chem. 2008 May 30;283(22):14915-26
references.pmid: 18400762
references.citation: Mol Biol Cell. 2007 Dec;18(12):4899-910
references.pmid: 17898081
references.citation: Mol Cell Biol. 2004 Mar;24(6):2499-512
references.pmid: 14993287
references.citation: J Cell Biol. 2008 Jun 16;181(6):985-98
references.pmid: 18541705
references.citation: Nature. 2009 Mar 5;458(7234):87-91
references.pmid: 19262673
references.citation: Cell. 2003 Feb 21;112(4):453-65
references.pmid: 12600310
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1484-9
references.pmid: 12552122
references.citation: Cell. 1995 Apr 7;81(1):53-62
references.pmid: 7536630
references.citation: Cancer Res. 2004 Dec 1;64(23):8585-94
references.pmid: 15574765
references.citation: Curr Biol. 2001 Mar 6;11(5):370-4
references.pmid: 11267876
references.citation: Curr Biol. 2007 Jun 19;17(12):R455-7
references.pmid: 17580073
references.citation: Cancer Cell. 2005 Feb;7(2):155-65
references.pmid: 15710328
references.citation: EMBO J. 2007 Oct 31;26(21):4597-606
references.pmid: 17914456
references.citation: J Cell Biol. 1996 Sep;134(6):1551-62
references.pmid: 8830782
references.citation: J Cell Biol. 2003 May 26;161(4):697-705
references.pmid: 12756237
references.citation: Mol Cell Biol. 2004 Sep;24(17):7578-97
references.pmid: 15314167
references.citation: Mol Biol Cell. 2007 Jul;18(7):2579-91
references.pmid: 17475772
references.citation: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12518-23
references.pmid: 10535954
references.citation: Curr Biol. 2004 Apr 20;14(8):697-703
references.pmid: 15084285
references.citation: Dev Cell. 2008 Dec;15(6):813-28
references.pmid: 19081071
references.citation: J Biol Chem. 2004 Mar 5;279(10):9565-76
references.pmid: 14676198
references.citation: J Biol Chem. 1999 Aug 13;274(33):23549-57
references.pmid: 10438535
references.citation: Mol Biol Cell. 2003 Feb;14(2):407-16
references.pmid: 12589043
references.citation: Curr Opin Cell Biol. 2008 Apr;20(2):235-41
references.pmid: 18337078
references.citation: Cell. 1991 Feb 22;64(4):693-702
references.pmid: 1997203
references.citation: Cancer Res. 2006 Mar 15;66(6):3034-43
references.pmid: 16540652
references.citation: J Cell Biol. 2008 Jan 28;180(2):427-41
references.pmid: 18227284
references.citation: J Cell Biol. 2005 Jan 31;168(3):441-52
references.pmid: 15684033
references.citation: Curr Opin Cell Biol. 2009 Feb;21(1):38-46
references.pmid: 19217273
references.citation: Cell. 1996 Oct 18;87(2):227-39
references.pmid: 8861907
references.citation: J Immunol. 2000 Jul 1;165(1):221-5
references.pmid: 10861055
references.citation: J Cell Sci. 1989 Sep;94 ( Pt 1):85-99
references.pmid: 2482298
references.citation: Mol Ther. 2006 Apr;13(4):729-37
references.pmid: 16360341
references.citation: J Cell Biol. 2000 Mar 6;148(5):957-70
references.pmid: 10704446
references.citation: J Clin Neurosci. 2008 Jul;15(7):725-37
references.pmid: 18468901
references.citation: Cell. 2006 Dec 1;127(5):1015-26
references.pmid: 17129785
references.citation: J Cell Biol. 1992 Nov;119(4):1003-13
references.pmid: 1385441
references.citation: Cell. 2006 Jun 30;125(7):1361-74
references.pmid: 16814721
references.citation: PLoS One. 2008;3(11):e3735
references.pmid: 19011687
references.citation: Annu Rev Cell Dev Biol. 2003;19:541-64
references.pmid: 14570581
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11933-8
references.pmid: 17606906
references.citation: Nat Cell Biol. 2006 Dec;8(12):1337-47
references.pmid: 17115031
references.citation: Eur J Cell Biol. 2008 Sep;87(8-9):491-506
references.pmid: 18417250
references.citation: Cell. 2007 Feb 9;128(3):561-75
references.pmid: 17289574
references.citation: Curr Biol. 2003 Mar 4;13(5):384-93
references.pmid: 12620186
references.citation: J Biol Chem. 2008 Jul 18;283(29):20454-72
references.pmid: 18448434
references.citation: J Cell Sci. 1993 Feb;104 ( Pt 2):595-606
references.pmid: 8505382
references.citation: Science. 2009 Jan 30;323(5914):638-41
references.pmid: 19179532
references.citation: Annu Rev Cell Dev Biol. 1996;12:463-518
references.pmid: 8970735
references.citation: Chemphyschem. 2004 Mar 19;5(3):383-8
references.pmid: 15067875
references.citation: J Biol Chem. 2000 Dec 29;275(52):41439-46
references.pmid: 11007774
references.citation: Mol Biol Cell. 2009 Feb;20(3):948-62
references.pmid: 19109420
references.citation: J Cell Biol. 2007 Mar 26;176(7):953-64
references.pmid: 17371834
references.citation: J Biol Chem. 2004 Apr 9;279(15):14929-36
references.pmid: 14752106
references.citation: J Cell Biol. 2008 Mar 10;180(5):957-71
references.pmid: 18332219
references.citation: Cancer Cell. 2005 Sep;8(3):241-54
references.pmid: 16169468
references.citation: J Bone Miner Res. 2006 Dec;21(12):1913-23
references.pmid: 17002556
references.citation: Cancer Res. 2007 May 1;67(9):4227-35
references.pmid: 17483334
references.citation: Am J Physiol Cell Physiol. 2001 Jun;280(6):C1669-79
references.pmid: 11350763
references.citation: Mol Cell Biol. 2007 Dec;27(23):8271-83
references.pmid: 17893324
references.citation: Curr Biol. 2008 Sep 9;18(17):1288-94
references.pmid: 18760605
references.citation: J Cell Biol. 2002 Dec 9;159(5):881-91
references.pmid: 12473693
references.citation: J Cell Biol. 2006 May 8;173(3):383-94
references.pmid: 16651381
references.citation: J Cell Sci. 2003 Dec 15;116(Pt 24):4915-24
references.pmid: 14625385
references.citation: J Cell Sci. 2008 Feb 1;121(Pt 3):379-90
references.pmid: 18198193
references.citation: J Cell Sci. 2006 May 1;119(Pt 9):1914-25
references.pmid: 16636076
references.citation: Biophys J. 2002 Sep;83(3):1380-94
references.pmid: 12202364
references.citation: Eur J Cell Biol. 2006 Apr;85(3-4):183-9
references.pmid: 16546560
references.citation: J Bone Miner Res. 2004 Mar;19(3):499-506
references.pmid: 15040839
references.citation: Science. 2007 Jan 5;315(5808):111-5
references.pmid: 17204653
references.citation: J Cell Sci. 2006 Feb 15;119(Pt 4):769-81
references.pmid: 16449321
references.citation: Biophys J. 1999 Apr;76(4):2307-16
references.pmid: 10096925
references.citation: J Cell Sci. 2008 Jul 15;121(Pt 14):2394-405
references.pmid: 18577577
references.citation: J Biol Chem. 2005 Aug 5;280(31):28653-62
references.pmid: 15939738
references.citation: EMBO J. 2003 Mar 3;22(5):1168-79
references.pmid: 12606581
references.citation: J Cell Sci. 2006 Aug 15;119(Pt 16):3316-24
references.pmid: 16868024
references.citation: J Cell Biol. 2007 Nov 5;179(3):553-65
references.pmid: 17967945
references.citation: Cell. 2000 Jun 23;101(7):717-28
references.pmid: 10892743
references.citation: Trends Cell Biol. 2006 May;16(5):257-63
references.pmid: 16581250
references.citation: J Cell Biol. 1992 Dec;119(5):1309-25
references.pmid: 1447304
references.citation: Cell. 2007 Mar 9;128(5):901-13
references.pmid: 17350575
references.citation: Curr Biol. 2002 Aug 6;12(15):1270-8
references.pmid: 12176354
references.citation: J Cell Biol. 2007 Sep 10;178(6):1053-64
references.pmid: 17846174
references.citation: Immunity. 2007 Jun;26(6):784-97
references.pmid: 17570692
references.citation: EMBO J. 2006 Jan 25;25(2):290-301
references.pmid: 16407977
references.citation: Biophys J. 2006 Nov 15;91(10):3907-20
references.pmid: 16920834
references.citation: J Cell Biol. 2000 Jul 24;150(2):377-89
references.pmid: 10908579
references.citation: Cell. 2004 Jul 23;118(2):203-16
references.pmid: 15260990
references.citation: Curr Biol. 2008 Sep 9;18(17):1295-1299
references.pmid: 18718759
references.citation: J Biol Chem. 2007 Mar 16;282(11):8446-53
references.pmid: 17229736
references.citation: Nat Cell Biol. 2008 Sep;10(9):1039-50
references.pmid: 19160484
references.citation: J Cell Sci. 2004 Jan 15;117(Pt 2):223-31
references.pmid: 14676275
references.citation: Blood. 2001 Aug 15;98(4):1142-9
references.pmid: 11493463
references.citation: Cell Adh Migr. 2009 Jul-Sep;3(3):288-92
references.pmid: 19458499
references.citation: J Biol Chem. 2008 May 16;283(20):13856-66
references.pmid: 18337256
references.citation: Am J Physiol Cell Physiol. 2000 Nov;279(5):C1345-50
references.pmid: 11029281
references.citation: Phys Med Biol. 2007 Mar 21;52(6):1565-76
references.pmid: 17327649
references.citation: Curr Biol. 2008 May 6;18(9):R362-4
references.pmid: 18460310