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Therapeutic Targeting of the Actin Cytoskeleton in Cancer

  • Teresa Bonello
  • Jason Coombes
  • Galina Schevzov
  • Peter Gunning
  • Justine Stehn
Chapter

Abstract

In cancer, actin filament populations and associated remodelling proteins are involved in driving proliferation, apoptosis and motility. Furthermore, a web of signalling pathways converge with the actin cytoskeleton to regulate these functions. Importantly, the actin cytoskeleton is a heterogeneous assembly of filament populations, each contributing to shared and unique cellular functions. The current range of actin-disrupting compounds are limited in their therapeutic use as they cannot discriminate between functionally specific populations of actin. Universal disruption of actin is likely to be intolerable in a clinical setting. Dissecting the regulation and composition of these filament populations will allow for treatments tailored to target the unique cytoskeletal repertoire of tumour cells. Identifying specific actin filament populations which are indispensible for tumour cell function is the focus of current work.

Keywords

Actin Filament Actin Cytoskeleton Mitochondrial Permeability Transition Pore Actin Assembly Pocket Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Pawlak G, Helfman DM (2001) Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Dev 11:41–47PubMedCrossRefGoogle Scholar
  2. 2.
    Helfman DM, Flynn P, Khan P, Saeed A (2008) Tropomyosin as a regulator of cancer cell transformation. Adv Exp Med Biol 644:124–131PubMedCrossRefGoogle Scholar
  3. 3.
    Allingham JS, Klenchin VA, Rayment I (2006) Actin-targeting natural products: structures, properties and mechanisms of action. Cell Mol Life Sci 63:2119–2134PubMedCrossRefGoogle Scholar
  4. 4.
    Fenteany G, Zhu S (2003) Small-molecule inhibitors of actin dynamics and cell motility. Curr Top Med Chem 3:593–616PubMedCrossRefGoogle Scholar
  5. 5.
    Bonello T, Stehn J, Gunning P (2009) New approaches to targeting the actin cytoskeleton for chemotherapy. Future Med Chem 1:1311–1331PubMedCrossRefGoogle Scholar
  6. 6.
    Hall A, Nobes CD (2000) Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Philos Trans R Soc Lond B Biol Sci 355:965–970PubMedCrossRefGoogle Scholar
  7. 7.
    Gunning P, O’Neill G, Hardeman E (2008) Tropomyosin-based regulation of the actin cytoskeleton in time and space. Physiol Rev 88:1–35PubMedCrossRefGoogle Scholar
  8. 8.
    Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501–1512PubMedCrossRefGoogle Scholar
  9. 9.
    Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677 (New York, N.Y.)PubMedCrossRefGoogle Scholar
  10. 10.
    Juliano R (1996) Cooperation between soluble factors and integrin-mediated cell anchorage in the control of cell growth and differentiation. BioEssays News Rev Mol Cell Dev Biol 18:911–917CrossRefGoogle Scholar
  11. 11.
    Massagué J (2004) G1 cell-cycle control and cancer. Nature 432:298–306PubMedCrossRefGoogle Scholar
  12. 12.
    Maness PF, Walsh RC (1982) Dihydrocytochalasin B disorganizes actin cytoarchitecture and inhibits initiation of DNA synthesis in 3T3 cells. Cell 30:253–262PubMedCrossRefGoogle Scholar
  13. 13.
    Takasuka T, Ishibashi S, Ide T (1987) Expression of cell-cycle-dependent genes in serum stimulated cells whose entry into S phase is blocked by cytochalasin D. Biochimica Et Biophysica Acta 909:161–164PubMedCrossRefGoogle Scholar
  14. 14.
    Takasuka T, Ishibashi S, Ide T (1987) GC-7 cells are growth arrested by cytochalasin D at two different points in the cell cycle. Exp Cell Res 173:287–293PubMedCrossRefGoogle Scholar
  15. 15.
    Huang S, Chen CS, Ingber DE (1998) Control of cyclin D1, p27(Kip1), and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. Mol Biol Cell 9:3179–3193PubMedGoogle Scholar
  16. 16.
    Senderowicz AM, Kaur G, Sainz E, Laing C, Inman WD, Rodríguez J, Crews P, Malspeis L, Grever MR, Sausville EA (1995) Jasplakinolide’s inhibition of the growth of prostate carcinoma cells in vitro with disruption of the actin cytoskeleton. J Natl Cancer Inst 87:46–51PubMedCrossRefGoogle Scholar
  17. 17.
    Fabian I, Shur I, Bleiberg I, Rudi A, Kashman Y, Lishner M (1995) Growth modulation and differentiation of acute myeloid leukemia cells by jaspamide. Exp Hematol 23:583–587PubMedGoogle Scholar
  18. 18.
    Boonstra J, Moes MJA (2005) Signal transduction and actin in the regulation of G1-phase progression. Crit Rev Eukaryot Gene Expr 15:255–276PubMedCrossRefGoogle Scholar
  19. 19.
    Böhmer RM, Scharf E, Assoian RK (1996) Cytoskeletal integrity is required throughout the mitogen stimulation phase of the cell cycle and mediates the anchorage-dependent expression of cyclin D1. Mol Biol Cell 7:101–111PubMedGoogle Scholar
  20. 20.
    Roberts PJ, Der CJ (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26:3291–3310PubMedCrossRefGoogle Scholar
  21. 21.
    den Hartigh JC, van Bergen en Henegouwen PM, Verkleij AJ, Boonstra J (1992) The EGF receptor is an actin-binding protein. J Cell Biol 119:349–355CrossRefGoogle Scholar
  22. 22.
    Diakonova M, Payrastre B, van Velzen AG, Hage WJ, van Bergen en Henegouwen PM, Boonstra J, Cremers FF, Humbel BM (1995) Epidermal growth factor induces rapid and transient association of phospholipase C-gamma 1 with EGF-receptor and filamentous actin at membrane ruffles of A431 cells. J Cell Sci 108(Pt 6):2499–2509PubMedGoogle Scholar
  23. 23.
    Rijken PJ, van Hal GJ, van der Heyden MA, Verkleij AJ, Boonstra J (1998) Actin polymerization is required for negative feedback regulation of epidermal growth factor-induced signal transduction. Exp Cell Res 243:254–262PubMedCrossRefGoogle Scholar
  24. 24.
    Payrastre B, van Bergen en Henegouwen PM, Breton M, den Hartigh JC, Plantavid M, Verkleij AJ, Boonstra J (1991) Phosphoinositide kinase, diacylglycerol kinase, and phospholipase C activities associated to the cytoskeleton: effect of epidermal growth factor. J Cell Biol 115:121–128PubMedCrossRefGoogle Scholar
  25. 25.
    Guinebault C, Payrastre B, Racaud-Sultan C, Mazarguil H, Breton M, Mauco G, Plantavid M, Chap H (1995) Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves specific interactions of p85 alpha with actin filaments and focal adhesion kinase. J Cell Biol 129:831–842PubMedCrossRefGoogle Scholar
  26. 26.
    Raymond E, Faivre S, Armand JP (2000) Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs 60(Suppl 1):15–23PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang H, Berezov A, Wang Q, Zhang G, Drebin J, Murali R, Greene MI (2007) ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest 117:2051–2058PubMedCrossRefGoogle Scholar
  28. 28.
    Roovers K, Assoian RK (2003) Effects of rho kinase and actin stress fibers on sustained extracellular signal-regulated kinase activity and activation of G(1) phase cyclin-dependent kinases. Mol Cell Biol 23:4283–4294PubMedCrossRefGoogle Scholar
  29. 29.
    Welsh CF, Assoian RK (2000) A growing role for Rho family GTPases as intermediaries in growth factor- and adhesion-dependent cell cycle progression. Biochimica Et Biophysica Acta 1471:M21–M29PubMedGoogle Scholar
  30. 30.
    Welsh CF, Roovers K, Villanueva J, Liu Y, Schwartz MA, Assoian RK (2001) Timing of cyclin D1 expression within G1 phase is controlled by Rho. Nat Cell Biol 3:950–957PubMedCrossRefGoogle Scholar
  31. 31.
    Walker JL, Fournier AK, Assoian RK (2005) Regulation of growth factor signaling and cell cycle progression by cell adhesion and adhesion-dependent changes in cellular tension. Cytokine Growth Factor Rev 16:395–405PubMedCrossRefGoogle Scholar
  32. 32.
    Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart-King CA, Margulies SS, Dembo M, Boettiger D, Hammer DA, Weaver VM (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell 8:241–254PubMedCrossRefGoogle Scholar
  33. 33.
    Reshetnikova G, Barkan R, Popov B, Nikolsky N, Chang LS (2000) Disruption of the actin cytoskeleton leads to inhibition of mitogen-induced cyclin E expression, Cdk2 phosphorylation, and nuclear accumulation of the retinoblastoma protein-related p107 protein. Exp Cell Res 259:35–53PubMedCrossRefGoogle Scholar
  34. 34.
    Huang S, Ingber DE (2002) A discrete cell cycle checkpoint in late G(1) that is cytoskeleton-dependent and MAP kinase (Erk)-independent. Exp Cell Res 275:255–264PubMedCrossRefGoogle Scholar
  35. 35.
    Inamdar GS, Madhunapantula SV, Robertson GP (2010) Targeting the MAPK pathway in melanoma: why some approaches succeed and other fail. Biochem Pharmacol 80:624–637PubMedCrossRefGoogle Scholar
  36. 36.
    Smalley KSM (2006) Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol Cancer Ther 5:1136–1144PubMedCrossRefGoogle Scholar
  37. 37.
    Ikeda S, Cunningham LA, Boggess D, Hawes N, Hobson CD, Sundberg JP, Naggert JK, Smith RS, Nishina PM (2003) Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Hum Mol Genet 12:1029–1037PubMedCrossRefGoogle Scholar
  38. 38.
    Lee Y-J, Keng PC (2005) Studying the effects of actin cytoskeletal destabilization on cell cycle by cofilin overexpression. Mol Biotechnol 31:1–10PubMedCrossRefGoogle Scholar
  39. 39.
    Tsai C-H, Chiu S-J, Liu C-C, Sheu T-J, Hsieh C-H, Keng PC, Lee Y-J (2009) Regulated expression of cofilin and the consequent regulation of p27(kip1) are essential for G(1) phase progression. Cell Cycle (Georgetown, Tex) 8:2365–2374PubMedCrossRefGoogle Scholar
  40. 40.
    Zou L, Ding Z, Roy P (2010) Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer cells partly through p27kip1 upregulation. J Cell Physiol 223:623–629PubMedGoogle Scholar
  41. 41.
    Percival JM, Thomas G, Cock TA, Gardiner EM, Jeffrey PL, Lin JJ, Weinberger RP, Gunning P (2000) Sorting of tropomyosin isoforms in synchronised NIH 3T3 fibroblasts: evidence for distinct microfilament populations. Cell Motil Cytoskeleton 47:189–208PubMedCrossRefGoogle Scholar
  42. 42.
    Stehn JR, Schevzov G, O’Neill GM, Gunning PW (2006) Specialisation of the tropomyosin composition of actin filaments provides new potential targets for chemotherapy. Curr Cancer Drug Targets 6:245–256PubMedCrossRefGoogle Scholar
  43. 43.
    Bharadwaj SS (2008) Inhibition of Nuclear Accumulation of Phosphorylated ERK by Tropomyosin-1–Mediated Cytoskeletal Reorganization. J Cancer Mol 4:139–144Google Scholar
  44. 44.
    Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231–241PubMedCrossRefGoogle Scholar
  45. 45.
    Franklin-Tong VE, Gourlay CW (2008) A role for actin in regulating apoptosis/programmed cell death: evidence spanning yeast, plants and animals. Biochem J 413:389–404PubMedCrossRefGoogle Scholar
  46. 46.
    Mashima T, Naito M, Tsuruo T (1999) Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis. Oncogene 18:2423–2430PubMedCrossRefGoogle Scholar
  47. 47.
    Utsumi T, Sakurai N, Nakano K, Ishisaka R (2003) C-terminal 15 kDa fragment of cytoskeletal actin is posttranslationally N-myristoylated upon caspase-mediated cleavage and targeted to mitochondria. FEBS Lett 539:37–44PubMedCrossRefGoogle Scholar
  48. 48.
    Gourlay CW, Carpp LN, Timpson P, Winder SJ, Ayscough KR (2004) A role for the actin cytoskeleton in cell death and aging in yeast. J Cell Biol 164:803–809PubMedCrossRefGoogle Scholar
  49. 49.
    Posey SC, Bierer BE (1999) Actin stabilization by jasplakinolide enhances apoptosis induced by cytokine deprivation. J Biol Chem 274:4259–4265PubMedCrossRefGoogle Scholar
  50. 50.
    Odaka C, Sanders ML, Crews P (2000) Jasplakinolide induces apoptosis in various transformed cell lines by a caspase-3-like protease-dependent pathway. Clin Diagn Lab Immunol 7:947–952PubMedGoogle Scholar
  51. 51.
    Martin SS, Ridgeway AG, Pinkas J, Lu Y, Reginato MJ, Koh EY, Michelman M, Daley GQ, Brugge JS, Leder P (2004) A cytoskeleton-based functional genetic screen identifies Bcl-xL as an enhancer of metastasis, but not primary tumor growth. Oncogene 23:4641–4645PubMedCrossRefGoogle Scholar
  52. 52.
    Leadsham JE, Kotiadis VN, Tarrant DJ, Gourlay CW (2010) Apoptosis and the yeast actin cytoskeleton. Cell Death Differ 17:754–762PubMedCrossRefGoogle Scholar
  53. 53.
    Chua BT, Volbracht C, Tan KO, Li R, Yu VC, Li P (2003) Mitochondrial translocation of cofilin is an early step in apoptosis induction. Nat Cell Biol 5:1083–1089PubMedCrossRefGoogle Scholar
  54. 54.
    Klamt F, Zdanov S, Levine RL, Pariser A, Zhang Y, Zhang B, Yu LR, Veenstra TD, Shacter E (2009) Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin. Nat Cell Biol 11:1241–1246PubMedCrossRefGoogle Scholar
  55. 55.
    Bernstein BW, Chen H, Boyle JA, Bamburg JR (2006) Formation of actin-ADF/cofilin rods transiently retards decline of mitochondrial potential and ATP in stressed neurons. Am J Physiol Cell Physiol 291:C828–C839PubMedCrossRefGoogle Scholar
  56. 56.
    Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, McGarry TJ, Kirschner MW, Koths K, Kwiatkowski DJ, Williams LT (1997) Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science 278:294–298PubMedCrossRefGoogle Scholar
  57. 57.
    Koya RC, Fujita H, Shimizu S, Ohtsu M, Takimoto M, Tsujimoto Y, Kuzumaki N (2000) Gelsolin inhibits apoptosis by blocking mitochondrial membrane potential loss and cytochrome c release. J Biol Chem 275:15343–15349PubMedCrossRefGoogle Scholar
  58. 58.
    Kusano H, Shimizu S, Koya RC, Fujita H, Kamada S, Kuzumaki N, Tsujimoto Y (2000) Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC. Oncogene 19:4807–4814PubMedCrossRefGoogle Scholar
  59. 59.
    Li GH, Arora PD, Chen Y, McCulloch CA, Liu P (2010) Multifunctional roles of gelsolin in health and diseases. Med Res Rev. doi:10.1002/med.20231Google Scholar
  60. 60.
    Tanaka M, Mullauer L, Ogiso Y, Fujita H, Moriya S, Furuuchi K, Harabayashi T, Shinohara N, Koyanagi T, Kuzumaki N (1995) Gelsolin: a candidate for suppressor of human bladder cancer. Cancer Res 55:3228–3232PubMedGoogle Scholar
  61. 61.
    Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13:555–562PubMedCrossRefGoogle Scholar
  62. 62.
    Bharadwaj S, Thanawala R, Bon G, Falcioni R, Prasad GL (2005) Resensitization of breast cancer cells to anoikis by tropomyosin-1: role of Rho kinase-dependent cytoskeleton and adhesion. Oncogene 24:8291–8303PubMedCrossRefGoogle Scholar
  63. 63.
    Puthalakath H, Villunger A, O’Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC, Strasser A (2001) Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 293:1829–1832PubMedCrossRefGoogle Scholar
  64. 64.
    Tang HL, Le AH, Lung HL (2006) The increase in mitochondrial association with actin precedes Bax translocation in apoptosis. Biochem J 396:1–5PubMedCrossRefGoogle Scholar
  65. 65.
    Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362–374PubMedCrossRefGoogle Scholar
  66. 66.
    Amann KJ, Pollard TD (2001) The Arp2/3 complex nucleates actin filament branches from the sides of pre-existing filaments. Nat Cell Biol 3:306–310PubMedCrossRefGoogle Scholar
  67. 67.
    Blanchoin L, Amann KJ, Higgs HN, Marchand JB, Kaiser DA, Pollard TD (2000) Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins. Nature 404:1007–1011PubMedCrossRefGoogle Scholar
  68. 68.
    Mullins RD, Heuser JA, Pollard TD (1998) The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proc Natl Acad Sci U S A 95:6181–6186PubMedCrossRefGoogle Scholar
  69. 69.
    DesMarais V, Macaluso F, Condeelis J, Bailly M (2004) Synergistic interaction between the Arp2/3 complex and cofilin drives stimulated lamellipod extension. J Cell Sci 117:3499–3510PubMedCrossRefGoogle Scholar
  70. 70.
    Ichetovkin I, Grant W, Condeelis J (2002) Cofilin produces newly polymerized actin filaments that are preferred for dendritic nucleation by the Arp2/3 complex. Curr Biol 12:79–84PubMedCrossRefGoogle Scholar
  71. 71.
    Bailly M, Ichetovkin I, Grant W, Zebda N, Machesky LM, Segall JE, Condeelis J (2001) The F-actin side binding activity of the Arp2/3 complex is essential for actin nucleation and lamellipod extension. Curr Biol 11:620–625PubMedCrossRefGoogle Scholar
  72. 72.
    Steffen A, Faix J, Resch GP, Linkner J, Wehland J, Small JV, Rottner K, Stradal TE (2006) Filopodia formation in the absence of functional WAVE- and Arp2/3-complexes. Mol Biol Cell 17:2581–2591PubMedCrossRefGoogle Scholar
  73. 73.
    Steffen A, Rottner K, Ehinger J, Innocenti M, Scita G, Wehland J, Stradal TE (2004) Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J 23:749–759PubMedCrossRefGoogle Scholar
  74. 74.
    Stradal TE, Rottner K, Disanza A, Confalonieri S, Innocenti M, Scita G (2004) Regulation of actin dynamics by WASP and WAVE family proteins. Trends Cell Biol 14:303–311PubMedCrossRefGoogle Scholar
  75. 75.
    Iwaya K, Oikawa K, Semba S, Tsuchiya B, Mukai Y, Otsubo T, Nagao T, Izumi M, Kuroda M, Domoto H, Mukai K (2007) Correlation between liver metastasis of the colocalization of actin-related protein 2 and 3 complex and WAVE2 in colorectal carcinoma. Cancer Sci 98:992–999PubMedCrossRefGoogle Scholar
  76. 76.
    Semba S, Iwaya K, Matsubayashi J, Serizawa H, Kataba H, Hirano T, Kato H, Matsuoka T, Mukai K (2006) Coexpression of actin-related protein 2 and Wiskott-Aldrich syndrome family verproline-homologous protein 2 in adenocarcinoma of the lung. Clin Cancer Res 12:2449–2454PubMedCrossRefGoogle Scholar
  77. 77.
    Yang LY, Tao YM, Ou DP, Wang W, Chang ZG, Wu F (2006) Increased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 correlated with poor prognosis of hepatocellular carcinoma. Clin Cancer Res 12:5673–5679PubMedCrossRefGoogle Scholar
  78. 78.
    Kurisu S, Suetsugu S, Yamazaki D, Yamaguchi H, Takenawa T (2005) Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells. Oncogene 24:1309–1319PubMedCrossRefGoogle Scholar
  79. 79.
    Laurila E, Savinainen K, Kuuselo R, Karhu R, Kallioniemi A (2009) Characterization of the 7q21-q22 amplicon identifies ARPC1 A, a subunit of the Arp2/3 complex, as a regulator of cell migration and invasion in pancreatic cancer. Genes Chromosomes Cancer 48:330–339PubMedCrossRefGoogle Scholar
  80. 80.
    Ghosh M, Song X, Mouneimne G, Sidani M, Lawrence DS, Condeelis JS (2004) Cofilin promotes actin polymerization and defines the direction of cell motility. Science 304:743–746PubMedCrossRefGoogle Scholar
  81. 81.
    Yamaguchi H, Condeelis J (2007) Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta 1773:642–652PubMedCrossRefGoogle Scholar
  82. 82.
    Mouneimne G, DesMarais V, Sidani M, Scemes E, Wang W, Song X, Eddy R, Condeelis J (2006) Spatial and temporal control of cofilin activity is required for directional sensing during chemotaxis. Curr Biol 16:2193–2205PubMedCrossRefGoogle Scholar
  83. 83.
    Mouneimne G, Soon L, DesMarais V, Sidani M, Song X, Yip SC, Ghosh M, Eddy R, Backer JM, Condeelis J (2004) Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation. J Cell Biol 166:697–708PubMedCrossRefGoogle Scholar
  84. 84.
    Wang W, Eddy R, Condeelis J (2007) The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer 7:429–440PubMedCrossRefGoogle Scholar
  85. 85.
    Wang W, Goswami S, Lapidus K, Wells AL, Wyckoff JB, Sahai E, Singer RH, Segall JE, Condeelis JS (2004) Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors. Cancer Res 64:8585–8594PubMedCrossRefGoogle Scholar
  86. 86.
    Svitkina TM, Bulanova EA, Chaga OY, Vignjevic DM, Kojima S, Vasiliev JM, Borisy GG (2003) Mechanism of filopodia initiation by reorganization of a dendritic network. J Cell Biol 160:409–421PubMedCrossRefGoogle Scholar
  87. 87.
    Vignjevic D, Kojima S, Aratyn Y, Danciu O, Svitkina T, Borisy GG (2006) Role of fascin in filopodial protrusion. J Cell Biol 174:863–875PubMedCrossRefGoogle Scholar
  88. 88.
    Li A, Dawson JC, Forero-Vargas M, Spence HJ, Yu X, Konig I, Anderson K, Machesky LM (2010) The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr Biol 20:339–345PubMedCrossRefGoogle Scholar
  89. 89.
    Qualtrough D, Singh K, Banu N, Paraskeva C, Pignatelli M (2009) The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro. Br J Cancer 101:1124–1129PubMedCrossRefGoogle Scholar
  90. 90.
    Hwang JH, Smith CA, Salhia B, Rutka JT (2008) The role of fascin in the migration and invasiveness of malignant glioma cells. Neoplasia 10:149–159PubMedCrossRefGoogle Scholar
  91. 91.
    Darnel AD, Behmoaram E, Vollmer RT, Corcos J, Bijian K, Sircar K, Su J, Jiao J, Alaoui-Jamali MA, Bismar TA (2009) Fascin regulates prostate cancer cell invasion and is associated with metastasis and biochemical failure in prostate cancer. Clin Cancer Res 15:1376–1383PubMedCrossRefGoogle Scholar
  92. 92.
    Hashimoto Y, Skacel M, Adams JC (2005) Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker? Int J Biochem Cell Biol 37:1787–1804PubMedCrossRefGoogle Scholar
  93. 93.
    Machesky LM, Li A (2010) Fascin: invasive filopodia promoting metastasis. Commun Integr Biol 3:263–270PubMedCrossRefGoogle Scholar
  94. 94.
    Chen L, Yang S, Jakoncic J, Zhang JJ, Huang XY (2010) Migrastatin analogues target fascin to block tumour metastasis. Nature 464:1062–1066PubMedCrossRefGoogle Scholar
  95. 95.
    Paul AS, Pollard TD (2009) Review of the mechanism of processive actin filament elongation by formins. Cell Motil Cytoskeleton 66:606–617PubMedCrossRefGoogle Scholar
  96. 96.
    Pellegrin S, Mellor H (2005) The Rho family GTPase Rif induces filopodia through mDia2. Curr Biol 15:129–133PubMedCrossRefGoogle Scholar
  97. 97.
    Peng J, Wallar BJ, Flanders A, Swiatek PJ, Alberts AS (2003) Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42. Curr Biol 13:534–545PubMedCrossRefGoogle Scholar
  98. 98.
    Yang C, Czech L, Gerboth S, Kojima S, Scita G, Svitkina T (2007) Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile cells. PLoS Biol 5:e317PubMedCrossRefGoogle Scholar
  99. 99.
    Di Vizio D, Kim J, Hager MH, Morello M, Yang W, Lafargue CJ, True LD, Rubin MA, Adam RM, Beroukhim R, Demichelis F, Freeman MR (2009) Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res 69:5601–5609PubMedCrossRefGoogle Scholar
  100. 100.
    Kitzing TM, Wang Y, Pertz O, Copeland JW, Grosse R (2010) Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC. Oncogene 29:2441–2448PubMedCrossRefGoogle Scholar
  101. 101.
    Zhu XL, Liang L, Ding YQ (2008) Overexpression of FMNL2 is closely related to metastasis of colorectal cancer. Int J Colorectal Dis 23:1041–1047PubMedCrossRefGoogle Scholar
  102. 102.
    Rizvi SA, Neidt EM, Cui J, Feiger Z, Skau CT, Gardel ML, Kozmin SA, Kovar DR (2009) Identification and characterization of a small molecule inhibitor of formin-mediated actin assembly. Chem Biol 16:1158–1168PubMedCrossRefGoogle Scholar
  103. 103.
    Lorenz M, Yamaguchi H, Wang Y, Singer RH, Condeelis J (2004) Imaging sites of N-wasp activity in lamellipodia and invadopodia of carcinoma cells. Curr Biol 14:697–703PubMedCrossRefGoogle Scholar
  104. 104.
    Yamaguchi H, Lorenz M, Kempiak S, Sarmiento C, Coniglio S, Symons M, Segall J, Eddy R, Miki H, Takenawa T, Condeelis J (2005) Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. J Cell Biol 168:441–452PubMedCrossRefGoogle Scholar
  105. 105.
    Oser M, Yamaguchi H, Mader CC, Bravo-Cordero JJ, Arias M, Chen X, Desmarais V, van Rheenen J, Koleske AJ, Condeelis J (2009) Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. J Cell Biol 186:571–587PubMedCrossRefGoogle Scholar
  106. 106.
    Uruno T, Liu J, Zhang P, Fan Y, Egile C, Li R, Mueller SC, Zhan X (2001) Activation of Arp2/3 complex-mediated actin polymerization by cortactin. Nat Cell Biol 3:259–266PubMedCrossRefGoogle Scholar
  107. 107.
    Weaver AM, Karginov AV, Kinley AW, Weed SA, Li Y, Parsons JT, Cooper JA (2001) Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr Biol 11:370–374PubMedCrossRefGoogle Scholar
  108. 108.
    Martinez-Quiles N, Ho HY, Kirschner MW, Ramesh N, Geha RS (2004) Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP. Mol Cell Biol 24:5269–5280PubMedCrossRefGoogle Scholar
  109. 109.
    Clark ES, Whigham AS, Yarbrough WG, Weaver AM (2007) Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res 67:4227–4235PubMedCrossRefGoogle Scholar
  110. 110.
    Artym VV, Zhang Y, Seillier-Moiseiwitsch F, Yamada KM, Mueller SC (2006) Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Cancer Res 66:3034–3043PubMedCrossRefGoogle Scholar
  111. 111.
    Webb BA, Jia L, Eves R, Mak AS (2007) Dissecting the functional domain requirements of cortactin in invadopodia formation. Eur J Cell Biol 86:189–206PubMedCrossRefGoogle Scholar
  112. 112.
    Li Y, Tondravi M, Liu J, Smith E, Haudenschild CC, Kaczmarek M, Zhan X (2001) Cortactin potentiates bone metastasis of breast cancer cells. Cancer Res 61:6906–6911PubMedGoogle Scholar
  113. 113.
    Chuma M, Sakamoto M, Yasuda J, Fujii G, Nakanishi K, Tsuchiya A, Ohta T, Asaka M, Hirohashi S (2004) Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma. J Hepatol 41:629–636PubMedCrossRefGoogle Scholar
  114. 114.
    Luo ML, Shen XM, Zhang Y, Wei F, Xu X, Cai Y, Zhang X, Sun YT, Zhan QM, Wu M, Wang MR (2006) Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance. Cancer Res 66:11690–11699PubMedCrossRefGoogle Scholar
  115. 115.
    Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR (2009) Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 10:778–790PubMedCrossRefGoogle Scholar
  116. 116.
    Ponti A, Machacek M, Gupton SL, Waterman-Storer CM, Danuser G (2004) Two distinct actin networks drive the protrusion of migrating cells. Science 305:1782–1786PubMedCrossRefGoogle Scholar
  117. 117.
    Vicente-Manzanares M, Zareno J, Whitmore L, Choi CK, Horwitz AF (2007) Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells. J Cell Biol 176:573–580PubMedCrossRefGoogle Scholar
  118. 118.
    Parsons JT, Horwitz AR, Schwartz MA (2010) Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol 11:633–643PubMedCrossRefGoogle Scholar
  119. 119.
    Bugyi B, Didry D, Carlier MF (2010) How tropomyosin regulates lamellipodial actin-based motility: a combined biochemical and reconstituted motility approach. EMBO J 29:14–26PubMedCrossRefGoogle Scholar
  120. 120.
    Gupton SL, Anderson KL, Kole TP, Fischer RS, Ponti A, Hitchcock-DeGregori SE, Danuser G, Fowler VM, Wirtz D, Hanein D, Waterman-Storer CM (2005) Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin. J Cell Biol 168:619–631PubMedCrossRefGoogle Scholar
  121. 121.
    Zheng Q, Safina A, Bakin AV (2008) Role of high-molecular weight tropomyosins in TGF-beta-mediated control of cell motility. Int J Cancer 122:78–90PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Teresa Bonello
    • 1
  • Jason Coombes
    • 1
  • Galina Schevzov
    • 1
  • Peter Gunning
    • 1
  • Justine Stehn
    • 2
    • 1
  1. 1.School of Medical SciencesUniversity of New South WalesSydneyAustralia
  2. 2.Department of Pharmacology, School of Medical Sciences, Oncology Research UnitUniversity of New South WalesSydneyAustralia

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