Advertisement

Tropomyosin pp 124-131 | Cite as

Tropomyosin as a Regulator of Cancer Cell Transformation

  • David M. Helfman
  • Patrick Flynn
  • Protiti Khan
  • Ali Saeed
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 644)

Abstract

Tropomyosins (Tms) are among the most studied structural proteins of the actin cytoskeleton that are implicated in neoplastic-specific alterations in actin filament organization. Decreased expression of specific nonmuscle Tm isoforms is commonly associated with the transformed phenotype. These changes in Tm expression appear to contribute to the rearrangement of microfilament bundles and morphological alterations, increased cell motility and oncogenic signaling properties of transformed cells. Below we review aspects of Tm biology as it specifically relates to transformation and cancer including its expression in culture models of transformed cells and human tumors, mechanisms that regulate Tm expression and the role of Tm in oncogenic signaling.

Keywords

Actin Cytoskeleton Myosin Light Chain Kinase Oncogenic Signaling Rous Sarcoma Virus Increase Cell Motility 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pollack R, Osborn M, Weber K. Patterns of organization of actin and myosin in normal and transformed cultured cells. Proc Natl Acad Sci USA 1975; 72:994–998.PubMedCrossRefGoogle Scholar
  2. 2.
    Goldman RD, Yerna MI, Schloss IA. Localization and organization of microfilaments and related proteins in normal and virus-transformed cells. J Supramolecular Struct 1976; 5:155–183.CrossRefGoogle Scholar
  3. 3.
    Wang H, Goldberg AR. Changes in microfilament organization and surface topography upon transformation of chick embryo fibroblasts with rous sarcoma virus. Proc Natl Acad Sci USA 1976; 73:4065–4069.PubMedCrossRefGoogle Scholar
  4. 4.
    Edelman G, Yahara I. Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus. Proc Natl Acad Sci USA 1976; 73:2047–2051.PubMedCrossRefGoogle Scholar
  5. 5.
    Vollett JJ, Brugge JS, Noonan CA et al. The role of SV40 gene A in the alteration of microfilaments in transformed cells. Exp Cell Res 1977; 105:119–126.CrossRefGoogle Scholar
  6. 6.
    Shin S, Freedman VH, Risser R et al. Tumorigenicty of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci USA 1975; 72:4435–4439.PubMedCrossRefGoogle Scholar
  7. 7.
    Hendricks M, Weintraub H. Tropomyosin is decreased in transformed cells. Proc Natl Acad Sci USA 1981; 78:5633–5637.PubMedCrossRefGoogle Scholar
  8. 8.
    Hendicks M, Weintraub H. Multiple tropomyosin polypeptides in chicken embryo fibroblasts: differential repression of transcription by Rous sarcoma virus transformation. Mol Cell Biol 1984; 4:1823–1833.Google Scholar
  9. 9.
    Leonardi CL, Warren RH, Rubin RW. Lack of tropomyosin correlates with the absence of stress fibers in transformed rat kidney cells. Biochem Biophys Acta 1982; 720:154–162.PubMedCrossRefGoogle Scholar
  10. 10.
    Matsumura F, Lin JJC, Yamashiro-Matsumura S et al. Differential expression of tropomyosin froms in the microfilaments isolated from normal and transformed rat cultured cells. J Biol Chem 1983; 258:13954–13964.PubMedGoogle Scholar
  11. 11.
    Cooper HL, Feuerstain N, Noda M et al. Suppression of tropomyosin synthesis, a common biochemical feature of oncogenesis by structurally diverse retroviral oncogenes. Mol Cell Biol 1985; 5:972–983.PubMedGoogle Scholar
  12. 12.
    Lin JHC, Helfman DM, Hughes SH et al. Tropomyosin isoforms in chicken embryo fibroblasts: purification, characterization and changes in Rous sarcoma virus-transformed cells. J Cell Biol 1985; 100:692–703.PubMedCrossRefGoogle Scholar
  13. 13.
    Leavitt I, Latter G, Lutomski L et al. Tropomyosin isoforms switching in tumorigenic human fibroblasts Mol Cell Biol 1986; 6:2721–2726.PubMedGoogle Scholar
  14. 14.
    Takenaga K, Nakamura Y, Sakiyama S. Differential expression of a tropomyosin isoforms in low-and high-metastatic Lewis lung carcinoma cells. Mol Cell Biol 1988; 8:3934–3937.PubMedGoogle Scholar
  15. 15.
    Takenaga K, Nakamura Y, Sayiyama S. Suppresion of synthesis of tropomyosin isoforms 2 in metastatic v-Ha-ras-transformed NIH 3T3 cells. Biochem Biophys Res Commun 1988; 157:1111–1116.PubMedCrossRefGoogle Scholar
  16. 16.
    Stehn JR, Schevzov G, O’Neill GM et al. Specialisation of the tropomyosin composition of actin filaments provides new potential targets for chemotherapy. Current Cancer Drug Targets 2006; 6:245–256.PubMedCrossRefGoogle Scholar
  17. 17.
    Franzen B, Linder S, Uryu K et al. Expression of tropomyosin isosforms in benign and malignant human breast lesions. Brit J Cancer 1996; 73:909–913.PubMedGoogle Scholar
  18. 18.
    Raval GN, Bharadwaj S, Levine EA et al. Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis, in primary breast tumors. Oncogene 2003; 22:6194–6203.PubMedCrossRefGoogle Scholar
  19. 19.
    Varga AE, Stourman NV, Zheng Q et al. Silencing of the tropomyosin-1 gene by DNA methylation alters tumor suppressor function of TGF-beta. Oncogene 2005; 22:5043–5052.CrossRefGoogle Scholar
  20. 20.
    Pawlak G, McGarvey TW, Nguyen TB et al. Alterations in tropomyosin isoform expression in human transitional cell carcinoma of the urinary bladder. Int J Cancer 2004; 110:368–373.PubMedCrossRefGoogle Scholar
  21. 21.
    Hughes JA, Cook-Yarborough CM, Chadwick NC et al. High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pedoatric and adult CNS tumors. Glia 2003; 42:25–35.PubMedCrossRefGoogle Scholar
  22. 22.
    Galloway PG, Likavec MJ, Perry G. Tropomyosin isoforms expression in normal and neoplastic astrocytes. Lab Invest 1990; 62:163–170.PubMedGoogle Scholar
  23. 23.
    Lin JL, Geng X, Bhattacharya SD et al. Isolation and sequencing of a novel tropomyosin isoforms preferentially associated with colon cancer. Gastroenterology 2002; 123:152–162.PubMedCrossRefGoogle Scholar
  24. 24.
    Katz ME, McCormick F. Signal transduction from multiple Ras effectors. Curr Opin Genet Dev 1997; 7:75–79.PubMedCrossRefGoogle Scholar
  25. 25.
    Shields JM, Pruitt K, McFall A et al. Understanding Ras: it ain’t over’ til it’s over. Trends Cell Biol 2000; 10:147–154.PubMedCrossRefGoogle Scholar
  26. 26.
    Janssen RAJ, Veenstra KG, Jonasch P et al. Ras-and Raf-induced down-modulation of nonmuscle tropomyosin are MEK-independent. J Biol Chem 1998; 273:32182–32186.PubMedCrossRefGoogle Scholar
  27. 27.
    Kim PN, Jonasch E, Mosterman BC et al. Radicicol suppresses transformation and restores tropomyosin-2 expression in both ras-and MEK-transformed cells without inhibiting the Raf/MEK/ERK signaling cascade. Cell Growth Differ 2001; 12:543–550.PubMedGoogle Scholar
  28. 28.
    Janssen RAJ, Kim PN, Mier JW et al. Overexpression of kinase suppressor of Ras upregulates the high-molecular weight tropomyosin isoforms in ras-transformed NIH 3T3 fibroblasts. Mol Cell Biol 2003; 23:1786–1797.PubMedCrossRefGoogle Scholar
  29. 29.
    Ljungdahl S, Linder S, Franzen B et al. Down-regulation of tropomyosin-2 expression in c-Jun-transformed rat fibroblasts involves induction of a MEK-1 dependent autocrine loop. Cell Growth Differ 1998; 9:565–573.PubMedGoogle Scholar
  30. 30.
    Shields JM, Mehta H, Pruitt K et al. Opposing roles of the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades in Ras-mediated downregulation of tropomyosin. Mol Cell Biol 2002; 22:2304–2317.PubMedCrossRefGoogle Scholar
  31. 31.
    Bakin AV, Rinehart C, Safina A et al. A critical role of tropomyosins in TGF-β regulation of the actin cytoskeleton and cell motility in epithelial cells. Mol Biol Cell 2004; 15:4682–4694.PubMedCrossRefGoogle Scholar
  32. 32.
    Bharadwaj S, Prasad GL. Tropomyosin-1, a novel suppressor of cellular transformation is downregulated by promoter methylation in cancer cells. Cancer Lett 2002; 183:205–213.PubMedCrossRefGoogle Scholar
  33. 33.
    Zhu S, Si ML, Wu H et al. Micro RNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1) J Biol Chem 2007; 282:14328–14336.PubMedCrossRefGoogle Scholar
  34. 34.
    Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapopotitic factor in human glioblastoma cells. Cancer Res 2005; 65:6029–6033.PubMedCrossRefGoogle Scholar
  35. 35.
    Roldo C, Missiaglia E, Hagan JP et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 2006; 24:4677–4684.PubMedCrossRefGoogle Scholar
  36. 36.
    Si ML, Zhu S, Wu H et al. miR-21-mdiated tumor growth Oncogene 2007; 26:2799–2803.PubMedCrossRefGoogle Scholar
  37. 37.
    Prasad SVN, Jayatilleke A, Madamanchi A et al. Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocrytosis. Nature Cell Biol 2005; 7:785–796.CrossRefGoogle Scholar
  38. 38.
    Houle F, Rousseau S, Morrice N et al. Extracellular signal-regulated kinase mediates phosphorylation of tropomyosin-1 to promote cytoskeleton remodeling in response to oxidative stress: impact on membrane blebbing. Mol Biol Cell 2003; 14:1418–1432.PubMedCrossRefGoogle Scholar
  39. 39.
    Houle F, Poirer A, Dumaresq et al. DAP kinase mediates the phosphorylation of tropomyosin-1 downstream of the ERK pathway, which regulates the formation of stress fibers in response to oxidative stress. J Cell Sci 2007; 120:3666–3677.PubMedCrossRefGoogle Scholar
  40. 40.
    Prasad GL, Fuldner RA, Cooper HL. Expression of transduced tropomyosin 1 cDNA suppresses neoplastic growth of cells transformed by the ras oncogene. Proc Natl Acad Sci USA 1993; 90:7039–7043.PubMedCrossRefGoogle Scholar
  41. 41.
    Prasad GL, Masuelli L, Raj MH et al. Suppression of src-induced transformed phenotype by expression of tropomyosin-1. Oncogene 1999; 18:2027–2031.PubMedCrossRefGoogle Scholar
  42. 42.
    Takenaga K, Masuda A. Restoration of microfilament bundle organization in v-raf-transformed NRK cells after transduction with tropomyosin 2 cDNA. Cancer Lett 1994; 87:47–53.PubMedCrossRefGoogle Scholar
  43. 43.
    Braverman RH, Cooper HL, Lee HS et al. Anti-oncogenic effects of tropomyosin: isoform specificity and importance of protein coding sequences. Oncogene 1996; 13:537–545.PubMedGoogle Scholar
  44. 44.
    Gimona M, Kazzaz J, Helfman DM. Forced expression of tropomyosin 2 or 3 in vi-Ki-ras-transformed fibroblasts results in distinct phenotypic effects. Proc Natl Acad Sci USA 1996; 93:9618–9623.PubMedCrossRefGoogle Scholar
  45. 45.
    Janssen RAJ, Mier JW. Tropomyosin-2 cDNA lacking the 3′ untranslated region riboregulator induces growth inhibition of v-Ki-ras-transformed fibroblasts. Mol Biol Cell 1997; 8:897–908.PubMedGoogle Scholar
  46. 46.
    Hashimoto Y, Shindo-Okada N, Tani M et al. Identification of genes differentially expressed in association with metastatic potential of K-1735 murine melanoma by messenger RNA differential display. Cancer Res 1996; 56:5266–5271.PubMedGoogle Scholar
  47. 47.
    Wang FL, Wang Y, Wong WK et al. Two differentially expressed genes in normal human prostate tissue and in carcinoma. Cancer Res 1996; 56:3634–3637.PubMedGoogle Scholar
  48. 48.
    Yager ML, Hughes JAI, Lovicu FJ et al. British J Cancer 2003; 89:860–863.CrossRefGoogle Scholar
  49. 49.
    Pawlak G, Helfman DM. Posttranscriptional down-regulation of ROCKI/Rho-kinase through an MEK-dependent pathway leads to cytoskeleton disruption in Ras-transformed fibroblasts. Mol Biol Cell 2002a; 13(1):336–347.PubMedCrossRefGoogle Scholar
  50. 50.
    Pawlak G, Helfman DM. MEK Mediates v-Src-induced disruption of the actin cytoskeleton via inactivation of the Rho-ROCK-LIM kinase pathway. J Biol Chem 2002b; 277:26927–26933.PubMedCrossRefGoogle Scholar
  51. 51.
    Lee S, Helfman DM. Cytoplasmic p21 Cip1 is involved in Ras-induced inhibition of the ROCK/LIMK/cofilin pathway. J Biol Chem 2004; 279:1885–1891.PubMedCrossRefGoogle Scholar
  52. 52.
    Sahai E, Olson MF, Marshall CJ. Cross-talk between ras and rho signalling pathways in transformation favors proliferation and increased motility. EMBO J 2001; 20:755–766.PubMedCrossRefGoogle Scholar
  53. 53.
    Vial E, Sahai E, Marshall CJ. ERK-MARK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell 2003; 4:67–79.PubMedCrossRefGoogle Scholar
  54. 54.
    Amano M, Ito M, Kimura K et al. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem 1996; 271:20246–20249.PubMedCrossRefGoogle Scholar
  55. 55.
    Kimura K, Ito M, Amano M et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 1996; 273:245–248.PubMedCrossRefGoogle Scholar
  56. 56.
    Bamburg JR. Proteins of the ADF/cofilin family:essential regulators of actin dynamics. Annu Rev Cell Dev Biol 1999; 15:185–230.PubMedCrossRefGoogle Scholar
  57. 57.
    Lee SW, Tomasetto C, Sager R. Positive selection of candidate tumor-suppressor genes by subtractive hybridization. Proc Natl Acad Sci USA 1991; 88:2825–2829.PubMedCrossRefGoogle Scholar
  58. 58.
    Shah V, Bharadwaj S, Kaibuchi K et al. Cytoskeletal organization in tropomyosin-mediated reversion of ras-transformation: evidence for Rho kinase pathway. Oncogene 2001; 20:2112–2121.PubMedCrossRefGoogle Scholar
  59. 59.
    Bharadwaj S, Thanawala R, Bon G et al. Resensitization of breast cancer cells to anoikis by tropomyosin 1: role of Rho-kinase-dependent cytoskeleton and adhesion. Oncogene 2005; 24:8291–8303.PubMedCrossRefGoogle Scholar
  60. 60.
    Mahadev K, Raval G, Bharadwaj S et al. Suppression of the transformed phenotype of breast cancer by tropomyosin-1. Exp Cell Res 2002; 279:40–51.PubMedCrossRefGoogle Scholar
  61. 61.
    Boyd J, Risinger JI, Wiseman RW et al. Regulation of microfilament organization and anchorage-independent growth by tropomyosin 1. Proc Natl Acad Sci USA 1996; 92:15534–11538.Google Scholar
  62. 62.
    Helfman DM, Pawlak G. Myosin light chain kinase and acto-myosin contractility modulate activation of the ERK cascade downstream of oncogenic Ras. J Cell Biochem 2005; 95:1069–1080.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • David M. Helfman
    • 1
  • Patrick Flynn
    • 2
  • Protiti Khan
    • 2
  • Ali Saeed
    • 2
  1. 1.Department of Cell Biology and Anatomy Sheila and David Fuente Graduate Program in Cancer Biology Sylvester Comprehensive Cancer Center Leonard M. Miller School of MedicineUniversity of MiamiMiamiUSA
  2. 2.Sheila and David Fuente Graduate Program in Cancer Biology Leonard M. Miller School of MedicineUniversity of MiamiMiamiUSA

Personalised recommendations