Skip to main content
SpringerLink
Log in

The Role of the Actin Cytoskeleton in Cancer and Its Potential Use as a Therapeutic Target

  • Chapter
The Cytoskeleton in Health and Disease

Abstract

The actin microfilament network is important for maintaining cell shape and function in eukaryotic cells. It has a multitude of roles in cellular processes such as cell adhesion, motility, cellular signalling, intracellular trafficking and cytokinesis. Alterations in the organisation of the cytoskeleton and changes in cellular morphology, motility and adhesiveness are characteristic features of transformed cancer cells. For this reason cytoskeletal microfilaments have become promising targets for chemotherapy. To date, no actin targeting drugs have been used in clinical trials due to the fact that they disrupt actin microfilaments in both non-tumour and tumour cells. To circumvent this problem, actin filament populations need to be targeted more specifically. Not all actin filaments are the same and there is growing evidence that within a cell there are different populations of actin filaments which are spatially organised into distinct cellular compartments each with a unique function. The structure and function of the actin cytoskeleton is primarily regulated by the associated actin binding proteins. Tropomyosin (Tm) is an intrinsic component of most actin filaments and over 40 isoforms have been identified in non-muscle cells. Tm isoforms are spatially segregated and current evidence suggests that they can specify the functional capacity of the actin microfilaments. Therefore the composition of these functionally distinct actin filaments may be important in determining the viability of a cancer cell. If actin filament populations can be discriminated from those of cardiac and skeletal muscle based on their tropomyosin composition then this becomes a powerful approach for anticancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Dominguez R, Holmes KC (2011) Actin structure and function. Annu Rev Biophys 40:169–186

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Pollard TD (1986) Rate constants for the reactions of ATP- and ADP-actin with the ends of actin filaments. J Cell Biol 103(6 Pt 2):2747–2754

    CAS  PubMed  Google Scholar 

  3. Pollard TD, Blanchoin L, Mullins RD (2000) Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annu Rev Biophys Biomol Struct 29:545–576

    CAS  PubMed  Google Scholar 

  4. Drenckhahn D, Pollard TD (1986) Elongation of actin filaments is a diffusion-limited reaction at the barbed end and is accelerated by inert macromolecules. J Biol Chem 261(27):12754–12758

    CAS  PubMed  Google Scholar 

  5. Carlier MF, Pantaloni D (1986) Direct evidence for ADP-Pi-F-actin as the major intermediate in ATP-actin polymerization. Rate of dissociation of Pi from actin filaments. Biochemistry 25(24):7789–7792

    CAS  PubMed  Google Scholar 

  6. Goley ED, Welch MD (2006) The ARP2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol 7(10):713–726

    CAS  PubMed  Google Scholar 

  7. 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(11):6181–6186

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Pollitt AY, Insall RH (2009) WASP and SCAR/WAVE proteins: the drivers of actin assembly. J Cell Sci 122(Pt 15):2575–2578

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wu C et al (2012) Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis. Cell 148(5):973–987

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Weaver AM et al (2002) Interaction of cortactin and N-WASp with Arp2/3 complex. Curr Biol 12(15):1270–1278

    CAS  PubMed  Google Scholar 

  11. Pruyne D et al (2002) Role of formins in actin assembly: nucleation and barbed-end association. Science 297(5581):612–615

    CAS  PubMed  Google Scholar 

  12. Higgs HN, Peterson KJ (2005) Phylogenetic analysis of the formin homology 2 domain. Mol Biol Cell 16(1):1–13

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Otomo T et al (2005) Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain. Nature 433(7025):488–494

    CAS  PubMed  Google Scholar 

  14. Seth A, Otomo C, Rosen MK (2006) Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLalpha and mDia1. J Cell Biol 174(5):701–713

    CAS  PubMed  PubMed Central  Google Scholar 

  15. McDowell JM et al (1996) Structure and evolution of the actin gene family in Arabidopsis thaliana. Genetics 142(2):587–602

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Gunning P, O’Neill G, Hardeman E (2008) Tropomyosin-based regulation of the actin cytoskeleton in time and space. Physiol Rev 88(1):1–35

    CAS  PubMed  Google Scholar 

  17. Li XE et al (2011) Tropomyosin position on F-actin revealed by EM reconstruction and computational chemistry. Biophys J 100(4):1005–1013

    CAS  PubMed  Google Scholar 

  18. Holmes KC, Lehman W (2008) Gestalt-binding of tropomyosin to actin filaments. J Muscle Res Cell Motil 29(6-8):213–219

    CAS  PubMed  Google Scholar 

  19. Schevzov G et al (2005) Tissue-specific tropomyosin isoform composition. J Histochem Cytochem 53(5):557–570

    CAS  PubMed  Google Scholar 

  20. Gunning PW et al (2005) Tropomyosin isoforms: divining rods for actin cytoskeleton function. Trends Cell Biol 15(6):333–341

    CAS  PubMed  Google Scholar 

  21. Creed SJ et al (2011) Tropomyosin isoform 3 promotes the formation of filopodia by regulating the recruitment of actin-binding proteins to actin filaments. Exp Cell Res 317(3):249–261

    CAS  PubMed  Google Scholar 

  22. Bryce NS et al (2003) Specification of actin filament function and molecular composition by tropomyosin isoforms. Mol Biol Cell 14(3):1002–1016

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Martin C, Gunning P (2008) Isoform sorting of tropomyosins. Adv Exp Med Biol 644:187–200

    CAS  PubMed  Google Scholar 

  24. Martin C, Schevzov G, Gunning P (2010) Alternatively spliced N-terminal exons in tropomyosin isoforms do not act as autonomous targeting signals. J Struct Biol 170(2):286–293

    CAS  PubMed  Google Scholar 

  25. Skoumpla K et al (2007) Acetylation regulates tropomyosin function in the fission yeast Schizosaccharomyces pombe. J Cell Sci 120(Pt 9):1635–1645

    CAS  PubMed  Google Scholar 

  26. Coulton AT et al (2010) The recruitment of acetylated and unacetylated tropomyosin to distinct actin polymers permits the discrete regulation of specific myosins in fission yeast. J Cell Sci 123(Pt 19):3235–3243

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Clayton JE et al (2010) Differential regulation of unconventional fission yeast myosins via the actin track. Curr Biol 20(16):1423–1431

    CAS  PubMed  Google Scholar 

  28. Skau CT, Kovar DR (2010) Fimbrin and tropomyosin competition regulates endocytosis and cytokinesis kinetics in fission yeast. Curr Biol 20(16):1415–1422

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Johnson M, East DA, Mulvihill DP (2014) Formins determine the functional properties of actin filaments in yeast. Curr Biol 24(13):1525–1530

    CAS  PubMed  Google Scholar 

  30. Sporn MB (1996) The war on cancer. Lancet 347(9012):1377–1381

    CAS  PubMed  Google Scholar 

  31. Lauffenburger DA, Horwitz AF (1996) Cell migration: a physically integrated molecular process. Cell 84(3):359–369

    CAS  PubMed  Google Scholar 

  32. Friedl P, Gilmour D (2009) Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol 10(7):445–457

    CAS  PubMed  Google Scholar 

  33. Charras G, Paluch E (2008) Blebs lead the way: how to migrate without lamellipodia. Nat Rev Mol Cell Biol 9(9):730–736

    CAS  PubMed  Google Scholar 

  34. Buccione R, Caldieri G, Ayala I (2009) Invadopodia: specialized tumor cell structures for the focal degradation of the extracellular matrix. Cancer Metastasis Rev 28(1-2):137–149

    PubMed  Google Scholar 

  35. Diz-Munoz A et al (2010) Control of directed cell migration in vivo by membrane-to-cortex attachment. PLoS Biol 8(11), e1000544

    PubMed  PubMed Central  Google Scholar 

  36. Abercrombie M, Heaysman JE, Pegrum SM (1970) The locomotion of fibroblasts in culture. II. “Ruffling”. Exp Cell Res 60(3):437–444

    CAS  PubMed  Google Scholar 

  37. Abercrombie M, Heaysman JE, Pegrum SM (1971) The locomotion of fibroblasts in culture. IV. Electron microscopy of the leading lamella. Exp Cell Res 67(2):359–367

    CAS  PubMed  Google Scholar 

  38. Svitkina TM, Borisy GG (1999) Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J Cell Biol 145(5):1009–1026

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Blanchoin L, Pollard TD, Hitchcock-DeGregori SE (2001) Inhibition of the Arp2/3 complex-nucleated actin polymerization and branch formation by tropomyosin. Curr Biol 11(16):1300–1304

    CAS  PubMed  Google Scholar 

  40. DesMarais V et al (2002) Spatial regulation of actin dynamics: a tropomyosin-free, actin-rich compartment at the leading edge. J Cell Sci 115(Pt 23):4649–4660

    CAS  PubMed  Google Scholar 

  41. Kis-Bicskei N et al (2013) Purification of tropomyosin Br-3 and 5NM1 and characterization of their interactions with actin. Cytoskeleton (Hoboken) 70(11):755–765

    CAS  Google Scholar 

  42. Hillberg L et al (2006) Tropomyosins are present in lamellipodia of motile cells. Eur J Cell Biol 85(5):399–409

    CAS  PubMed  Google Scholar 

  43. Chesarone MA, DuPage AG, Goode BL (2010) Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol 11(1):62–74

    CAS  PubMed  Google Scholar 

  44. Ponti A et al (2004) Two distinct actin networks drive the protrusion of migrating cells. Science 305(5691):1782–1786

    CAS  PubMed  Google Scholar 

  45. Danuser G (2005) Coupling the dynamics of two actin networks—new views on the mechanics of cell protrusion. Biochem Soc Trans 33(Pt 6):1250–1253

    CAS  PubMed  Google Scholar 

  46. Vallotton P, Small JV (2009) Shifting views on the leading role of the lamellipodium in cell migration: speckle tracking revisited. J Cell Sci 122(Pt 12):1955–1958

    CAS  PubMed  Google Scholar 

  47. Bresnick AR (1999) Molecular mechanisms of nonmuscle myosin-II regulation. Curr Opin Cell Biol 11(1):26–33

    CAS  PubMed  Google Scholar 

  48. Burridge K, Chrzanowska-Wodnicka M (1996) Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol 12:463–518

    CAS  PubMed  Google Scholar 

  49. Fanning AS et al (1994) Differential regulation of skeletal muscle myosin-II and brush border myosin-I enzymology and mechanochemistry by bacterially produced tropomyosin isoforms. Cell Motil Cytoskeleton 29(1):29–45

    CAS  PubMed  Google Scholar 

  50. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    CAS  PubMed  Google Scholar 

  51. Friedl P (2004) Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol 16(1):14–23

    CAS  PubMed  Google Scholar 

  52. Behrens J et al (1989) Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell–cell adhesion. J Cell Biol 108(6):2435–2447

    CAS  PubMed  Google Scholar 

  53. Pollack R, Osborn M, Weber K (1975) Patterns of organization of actin and myosin in normal and transformed cultured cells. Proc Natl Acad Sci U S A 72(3):994–998

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Shin SI et al (1975) Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci U S A 72(11):4435–4439

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Braverman RH et al (1996) Anti-oncogenic effects of tropomyosin: isoform specificity and importance of protein coding sequences. Oncogene 13(3):537–545

    CAS  PubMed  Google Scholar 

  56. Gimona M, Kazzaz JA, Helfman DM (1996) Forced expression of tropomyosin 2 or 3 in v-Ki-ras-transformed fibroblasts results in distinct phenotypic effects. Proc Natl Acad Sci U S A 93(18):9618–9623

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Janssen RA, Mier JW (1997) Tropomyosin-2 cDNA lacking the 3′ untranslated region riboregulator induces growth inhibition of v-Ki-ras-transformed fibroblasts. Mol Biol Cell 8(5):897–908

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Yager ML et al (2003) Functional analysis of the actin-binding protein, tropomyosin 1, in neuroblastoma. Br J Cancer 89(5):860–863

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Prasad GL, Fuldner RA, Cooper HL (1993) Expression of transduced tropomyosin 1 cDNA suppresses neoplastic growth of cells transformed by the ras oncogene. Proc Natl Acad Sci U S A 90(15):7039–7043

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Takenaga K, Masuda A (1994) Restoration of microfilament bundle organization in v-raf-transformed NRK cells after transduction with tropomyosin 2 cDNA. Cancer Lett 87(1):47–53

    CAS  PubMed  Google Scholar 

  61. Bonello TT, Stehn JR, Gunning PW (2009) New approaches to targeting the actin cytoskeleton for chemotherapy. Future Med Chem 1(7):1311–1331

    CAS  PubMed  Google Scholar 

  62. Helfman DM et al (2008) Tropomyosin as a regulator of cancer cell transformation. Adv Exp Med Biol 644:124–131

    CAS  PubMed  Google Scholar 

  63. Franzen B et al (1996) Expression of tropomyosin isoforms in benign and malignant human breast lesions. Br J Cancer 73(7):909–913

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Wang FL et al (1996) Two differentially expressed genes in normal human prostate tissue and in carcinoma. Cancer Res 56(16):3634–3637

    CAS  PubMed  Google Scholar 

  65. Jung MH et al (2000) Identification of differentially expressed genes in normal and tumor human gastric tissue. Genomics 69(3):281–286

    CAS  PubMed  Google Scholar 

  66. O’Neill GM, Stehn J, Gunning PW (2008) Tropomyosins as interpreters of the signalling environment to regulate the local cytoskeleton. Semin Cancer Biol 18(1):35–44

    PubMed  Google Scholar 

  67. Alaiya AA et al (1997) Phenotypic analysis of ovarian carcinoma: polypeptide expression in benign, borderline and malignant tumors. Int J Cancer 73(5):678–683

    CAS  PubMed  Google Scholar 

  68. Alaiya AA et al (2001) Identification of proteins in human prostate tumor material by two-dimensional gel electrophoresis and mass spectrometry. Cell Mol Life Sci 58(2):307–311

    CAS  PubMed  Google Scholar 

  69. Takenaga K, Nakamura Y, Sakiyama S (1988) Differential expression of a tropomyosin isoform in low- and high-metastatic Lewis lung carcinoma cells. Mol Cell Biol 8(9):3934–3937

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Takenaga K et al (1988) Isolation and characterization of a cDNA that encodes mouse fibroblast tropomyosin isoform 2. Mol Cell Biol 8(12):5561–5565

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Stehn JR et al (2006) Specialisation of the tropomyosin composition of actin filaments provides new potential targets for chemotherapy. Curr Cancer Drug Targets 6(3):245–256

    CAS  PubMed  Google Scholar 

  72. Stehn JR et al (2013) A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells. Cancer Res 73(16):5169–5182

    CAS  PubMed  Google Scholar 

  73. Ljungdahl S et al (1998) Down-regulation of tropomyosin-2 expression in c-Jun-transformed rat fibroblasts involves induction of a MEK1-dependent autocrine loop. Cell Growth Differ 9(7):565–573

    CAS  PubMed  Google Scholar 

  74. Cooper HL et al (1985) Suppression of tropomyosin synthesis, a common biochemical feature of oncogenesis by structurally diverse retroviral oncogenes. Mol Cell Biol 5(5):972–983

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Shields JM et al (2002) Opposing roles of the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades in Ras-mediated downregulation of tropomyosin. Mol Cell Biol 22(7):2304–2317

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Matsumura F et al (1983) Differential expression of tropomyosin forms in the microfilaments isolated from normal and transformed rat cultured cells. J Biol Chem 258(22):13954–13964

    CAS  PubMed  Google Scholar 

  77. Hendricks M, Weintraub H (1981) Tropomyosin is decreased in transformed cells. Proc Natl Acad Sci U S A 78(9):5633–5637

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Lin JJ et al (1985) Tropomyosin isoforms in chicken embryo fibroblasts: purification, characterization, and changes in Rous sarcoma virus-transformed cells. J Cell Biol 100(3):692–703

    CAS  PubMed  Google Scholar 

  79. Prasad SC et al (1997) Protein expression changes associated with radiation-induced neoplastic progression of human prostate epithelial cells. Electrophoresis 18(3-4):629–637

    CAS  PubMed  Google Scholar 

  80. Leavitt J et al (1986) Tropomyosin isoform switching in tumorigenic human fibroblasts. Mol Cell Biol 6(7):2721–2726

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Bhattacharya B et al (1990) Tropomyosins of human mammary epithelial cells: consistent defects of expression in mammary carcinoma cell lines. Cancer Res 50(7):2105–2112

    CAS  PubMed  Google Scholar 

  82. Smith L et al (2007) The proteomic analysis of cisplatin resistance in breast cancer cells. Oncol Res 16(11):497–506

    CAS  PubMed  Google Scholar 

  83. Yang W et al (2013) Genetic and epigenetic alterations are involved in the regulation of TPM1 in cholangiocarcinoma. Int J Oncol 42(2):690–698

    CAS  PubMed  Google Scholar 

  84. Moghanibashi M et al (2012) Proteomics of a new esophageal cancer cell line established from Persian patient. Gene 500(1):124–133

    CAS  PubMed  Google Scholar 

  85. Zare M et al (2012) Downregulation of tropomyosin-1 in squamous cell carcinoma of esophagus, the role of Ras signaling and methylation. Mol Carcinog 51(10):796–806

    CAS  PubMed  Google Scholar 

  86. Kuramitsu Y et al (2010) Proteomic differential display analysis shows up-regulation of 14-3-3 sigma protein in human scirrhous-type gastric carcinoma cells. Anticancer Res 30(11):4459–4465

    CAS  PubMed  Google Scholar 

  87. Assinder SJ et al (2010) A novel splice variant of the beta-tropomyosin (TPM2) gene in prostate cancer. Mol Carcinog 49(6):525–531

    CAS  PubMed  Google Scholar 

  88. Jiang D et al (2003) Identification of metastasis-associated proteins by proteomic analysis and functional exploration of interleukin-18 in metastasis. Proteomics 3(5):724–737

    CAS  PubMed  Google Scholar 

  89. Hayashi E et al (2005) Proteomic profiling for cancer progression: differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines. Proteomics 5(4):1024–1032

    CAS  PubMed  Google Scholar 

  90. Hughes JA et al (2003) High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors. Glia 42(1):25–35

    PubMed  Google Scholar 

  91. Raval GN et al (2003) Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis, in primary breast tumors. Oncogene 22(40):6194–6203

    CAS  PubMed  Google Scholar 

  92. Kabbage M et al (2013) Tropomyosin-4 correlates with higher SBR grades and tubular differentiation in infiltrating ductal breast carcinomas: an immunohistochemical and proteomics-based study. Tumour Biol 34(6):3593–3602

    CAS  PubMed  Google Scholar 

  93. Lomnytska MI et al (2011) Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value. Br J Cancer 104(1):110–119

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Bae SM et al (2005) Two-dimensional gel analysis of protein expression profile in squamous cervical cancer patients. Gynecol Oncol 99(1):26–35

    CAS  PubMed  Google Scholar 

  95. Luo YX et al (2009) Identification of cancer-associated proteins by proteomics and downregulation of beta-tropomyosin expression in colorectal adenoma and cancer. Proteomics Clin Appl 3(12):1397–1406

    CAS  PubMed  Google Scholar 

  96. Lin JL et al (2002) Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. Gastroenterology 123(1):152–162

    CAS  PubMed  Google Scholar 

  97. Kim HJ et al (2012) Profiling of differentially expressed proteins in stage IV colorectal cancers with good and poor outcomes. J Proteomics 75(10):2983–2997

    CAS  PubMed  Google Scholar 

  98. Adami R et al (2003) On the stiffness of the natural actin filament decorated with alexa fluor tropomyosin. Biophys Chem 104(2):469–476

    CAS  PubMed  Google Scholar 

  99. Harada T et al (2007) Expression of tropomyosin alpha 4 chain is increased in esophageal squamous cell carcinoma as evidenced by proteomic profiling by two-dimensional electrophoresis and liquid chromatography–mass spectrometry/mass spectrometry. Proteomics Clin Appl 1(2):215–223

    CAS  PubMed  Google Scholar 

  100. Zhang J et al (2011) Using proteomic approach to identify tumor-associated proteins as biomarkers in human esophageal squamous cell carcinoma. J Proteome Res 10(6):2863–2872

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Qi Y et al (2005) Comparative proteomic analysis of esophageal squamous cell carcinoma. Proteomics 5(11):2960–2971

    CAS  PubMed  Google Scholar 

  102. Kawai A et al (2008) Global protein-expression analysis of bone and soft tissue sarcomas. Clin Orthop Relat Res 466(9):2099–2106

    PubMed  PubMed Central  Google Scholar 

  103. He QY et al (2004) Identification of tumor-associated proteins in oral tongue squamous cell carcinoma by proteomics. Proteomics 4(1):271–278

    CAS  PubMed  Google Scholar 

  104. Kim TM et al (2008) Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q. Int J Cancer 123(12):2808–2815

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Choi HS et al (2010) Tropomyosin3 overexpression and a potential link to epithelial–mesenchymal transition in human hepatocellular carcinoma. BMC Cancer 10:122

    PubMed  PubMed Central  Google Scholar 

  106. Suehara Y et al (2006) Proteomic signatures corresponding to histological classification and grading of soft-tissue sarcomas. Proteomics 6(15):4402–4409

    CAS  PubMed  Google Scholar 

  107. Deng B et al (2005) Proteomics analysis of stage-specific proteins expressed in human squamous cell lung carcinoma tissues. Cancer Biomark 1(6):279–286

    CAS  PubMed  Google Scholar 

  108. Lo WY et al (2007) Identification of over-expressed proteins in oral squamous cell carcinoma (OSCC) patients by clinical proteomic analysis. Clin Chim Acta 376(1-2):101–107

    CAS  PubMed  Google Scholar 

  109. Chow SN et al (2010) Analysis of protein profiles in human epithelial ovarian cancer tissues by proteomic technology. Eur J Gynaecol Oncol 31(1):55–62

    CAS  PubMed  Google Scholar 

  110. Ahram M et al (2002) Proteomic analysis of human prostate cancer. Mol Carcinog 33(1):9–15

    CAS  PubMed  Google Scholar 

  111. Hwa JS et al (2005) Identification of proteins differentially expressed in the conventional renal cell carcinoma by proteomic analysis. J Korean Med Sci 20(3):450–455

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Pawlak G et al (2004) Alterations in tropomyosin isoform expression in human transitional cell carcinoma of the urinary bladder. Int J Cancer 110(3):368–373

    CAS  PubMed  Google Scholar 

  113. Hellman K et al (2004) Protein expression patterns in primary carcinoma of the vagina. Br J Cancer 91(2):319–326

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Bailey MJ et al (2013) Stage-specific analysis of plasma protein profiles in ovarian cancer: difference in-gel electrophoresis analysis of pooled clinical samples. J Carcinog 12:10

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Oncology Research Unit, School of Medical Sciences, UNSW Australia, Room 229, Wallace Wurth East, Sydney, 2052, NSW, Australia

    Simon Brayford, Galina Schevzov, Julien Vos & Peter Gunning

Authors
  1. Simon Brayford
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Galina Schevzov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julien Vos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Gunning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Gunning .

Editor information

Editors and Affiliations

  1. Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, Missouri, USA

    Heide Schatten

Appendix: Table

Appendix: Table

Cell type

Tm isoform expressiona

References

 

Decreased

Increased

Unaltered

 

Experimentally transformed cells:

Jun-transformed rat fibroblasts

Tm2

  

[73]

Ras-transformed NIH3T3

Tm1–3

 

Tm4,5

[59, 74]

Ras-transformed rat intestinal epithelial cell

α-Tm

  

[75]

REF-52 transformed with DNA or RNA virus

Tm1

Tm3,5

 

[76]

RSV-transformed NRK

Tm1,2

Tm4,5

 

[76]

RSV-transformed chick embryo fibroblasts

(α and β) Tm1

  

[77, 78]

Src-transformed NIH3T3

Tm1

  

[76]

Transformed/tumorigenic 267B1 prostate cell

Tm1,3

  

[79]

Transformed HUT-12 fibroblasts

Tm1,2,6

 

Tm4,5

[80]

Transformed HUT-14 fibroblasts

Tm1,2,3,4,6

 

Tm5

[80]

Tumorigenic HUT-14T fibroblasts

Tm1,2,3,4,6

 

Tm5

[80]

Tumor derived HOS

Tm1,2,6

Tm5

Tm4

[80]

Cultured cancer cell lines:

Breast carcinoma cell lines:

BT-20

Tm1

Tm5, Tm32b

 

[81]

BT-474

Tm1, Tm38b

  

[81]

MCF7

Tm1, Tm38b

Tm3,4,32b

 

[81]

MDA-MB-231

Tm1

Tm4,5,32b

 

[81]

Novel MCF7 cisplatin resistant

Tm1c

  

[82]

T47D

Tm1

Tm3,36b

 

[81]

ZR-75.1

Tm1,38b

Tm5,32b

 

[81]

Cholangiocarcinoma cell lines:

HuCCT1

Tm1

  

[83]

QBC939

 

Tm1

 

[83]

Esophageal carcinoma cell lines:

Novel esophagus squamous cancer cell line

 

Tm3

 

[84]

TE15

Tm1–3

  

[85]

Gastric carcinoma cell lines:

OCUM-1

 

Tm4

 

[86]

OCUM-2D

 

Tm4

 

[86]

OCUM-2M

 

Tm4

 

[86]

OCUM-2MLN

 

Tm4

 

[86]

OCUM-D3

 

Tm4

 

[86]

OCUM-9

 

Tm4

 

[86]

OCUM-12

 

Tm4

 

[86]

Neuroblastoma cell lines:

IMR32

Tm1–3, 5a,5b

  

[58]

BE(2)-C

Tm1–3, 5a,5b

  

[58]

Prostate cell lines:

DU-145

Tm1

Novel β-Tmf

 

[64, 87]

LNCaP

Tm1

Novel β-Tmf

 

[64, 87]

PC3

Tm1

Novel β-Tmf

 

[64, 87]

DLD-1 human colon cancer cell line

α-Tm

  

[75]

Tumor derived HT1080 fibrosarcoma

Tm2,6

Tm5

Tm4

[75, 80]

Lewis lung carcinoma cell line

Tm2

  

[69]

PLA801D non-small cell lung carcinoma cell line

 

Tm3d

 

[88]

QRsP-11 fibrosarcoma cell line

 

Tm1e

 

[89]

Patient tumor material:

Astrocytoma (high grade)

HMW Tm

  

[90]

Breast carcinoma:

Tm1–3

  

[63, 91]

Infiltrating ductal breast carcinoma

 

Tm4

 

[92]

Cervical carcinoma

Tm1,2,4

Tm3

 

[93–95]

Colon cancer

β-Tmg

TC22f, Tm2h

 

[95–97]

Esophageal cancer

β-Tm, Tm1

α-Tm, Tm4

 

[98–101]

Fibrous histiocytoma

 

Tm3,4

 

[65, 102]

Gastric carcinoma

α-Tm

LMW Tm

 

[65, 103]

Hepatocellular carcinoma

 

Tm5

 

[104, 105]

Leiomyosarcoma:

Pleomorphic leiomyosarcoma

Tm1,2

Tm3,4

 

[102, 106]

Conventional leiomyosarcoma

Tm3,4

Tm1,2

 

[102, 106]

Lung carcinoma (high grade)

Tm3i

  

[107]

Oral squamous cell carcinoma

 

Tm2

 

[108]

Oral tongue squamous cell carcinoma

Tm1

LMW Tm

 

[103]

Ovarian carcinoma

Tm2,4

  

[67, 109]

Prostate cancer

Tm1

  

[64, 110]j

Renal cell carcinoma

Tm4

  

[111]

Transitional bladder cell carcinoma

Tm1–3

Tm5

 

[112]

Vaginal carcinoma

Tm1

  

[113]

Patient plasma material:

Ovarian carcinoma

 

Tm4k

 

[114]

  1. aDecreased expression refers to down-regulation or loss of isoform specific protein or mRNA and increased expression correspondingly refers to the gain of protein or mRNA
  2. bNone of the isoforms corresponded to previously identified isoforms expressed in fibroblasts
  3. cDown-regulation of Tm1 compared to the MCF7 breast cancer cell line
  4. dUp-regulation of Tm3 in the highly metastatic PLA801D subline compared to the poorly metastatic PLA801C subline
  5. eUp-regulation of Tm1 in the progressive cancer cell line QRsP-11 compared to the regressive cell line QR-32
  6. fA novel Tm isoform
  7. gDown-regulation of β-Tm was also found in colorectal adenoma tissue
  8. hTm2 was found to be increased in patients with poor outcome compared to patients with good outcome
  9. iTm3 showed a steady decline with the malignant progression of squamous cell lung carcinoma from stage I to stage IV
  10. jDown-regulation of β-Tm was observed in only one of the tumors (high grade) assayed
  11. kExpression of Tm4 showed an early increase in the first stages of ovarian cancer, followed by a steady decrease in later stages

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Brayford, S., Schevzov, G., Vos, J., Gunning, P. (2015). The Role of the Actin Cytoskeleton in Cancer and Its Potential Use as a Therapeutic Target. In: Schatten, H. (eds) The Cytoskeleton in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2904-7_16

Download citation

Publish with us

Policies and ethics

Search

Navigation