Biochemistry (Moscow)

, Volume 77, Issue 11, pp 1266–1276 | Cite as

Actin isoforms and reorganization of adhesion junctions in epithelial-to-mesenchymal transition of cervical carcinoma cells

  • G. S. Shagieva
  • L. V. Domnina
  • T. A. Chipysheva
  • V. D. Ermilova
  • C. Chaponnier
  • V. B. DuginaEmail author


Malignant cell transformation requires changes in the ability of cells to migrate. The disruption of actin cytoskeleton and intercellular adhesions is an important component of the acquisition of invasive properties in epithelial malignancies. The invasive ability of carcinoma cells is associated with reduced expression of adhesion junction molecules and increased expression of mesenchymal markers, frequently referred to as epithelial-to-mesenchymal transition (EMT). Standard features of the EMT program in cancer cells include fibroblastic phenotype, downregulation of the epithelial marker E-cadherin, induction of Snail-family transcription factors, as well as expression of mesenchymal proteins. We compared the epithelial and mesenchymal marker profiles of nonmalignant HaCaT keratinocytes to the corresponding profiles of cervical carcinoma cell lines C-33A, SiHa, and CaSki. The characteristics of the EMT appeared to be more developed in SiHa and CaSki cervical cancer cells. Further activation of the EMT program in cancer cells was induced by epidermal growth factor. Decreased epithelial marker E-cadherin in CaSki cells was accompanied by increased mesenchymal markers N-cadherin and vimentin. Downregulated expression of E-cadherin in SiHa and CaSki cells was associated with increased expression of Snail transcription factor. Our goal was to study actin reorganization in the EMT process in cell cultures and in tissue. We found that β-cytoplasmic actin structures are disorganized in the cervical cancer cells. The expression of β-cytoplasmic actin was downregulated.

Key words

epithelial-to-mesenchymal transition E-cadherin cervical carcinoma cytoplasmic actin isoforms 



epidermal growth factor


epithelial-to-mesenchymal transition


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  1. 1.
    Acloque, H., Adams, M. S., Fishwick, K., Bronner-Fraser, M., and Nieto, M. A. (2009) J. Clin. Invest., 119, 1438–1449.PubMedCrossRefGoogle Scholar
  2. 2.
    Lee, J. M., Dedhar, S., Kalluri, R., and Thompson, E. W. (2006) J. Cell Biol., 172, 973–981.PubMedCrossRefGoogle Scholar
  3. 3.
    Moustakas, A., and Heldin, C.-H. (2007) Cancer Sci., 98, 1512–1520.PubMedCrossRefGoogle Scholar
  4. 4.
    Zeisberg, M., and Neilson, E. G. (2009) J. Clin. Invest., 119, 1429–1437.PubMedCrossRefGoogle Scholar
  5. 5.
    Thiery, J. P. (2002) Nat. Rev. Cancer, 2, 442–454.PubMedCrossRefGoogle Scholar
  6. 6.
    Friedl, P. (2004) Curr. Opin. Cell Biol., 16, 14–23.PubMedCrossRefGoogle Scholar
  7. 7.
    Brockmann, C., Huarte, J., Dugina, V., Challet, L., Rey, E., Conne, B., Swetloff, A., Nef, S., Chaponnier, C., and Vassalli, J. D. (2011) Biol. Reprod., 85, 1025–1039.PubMedCrossRefGoogle Scholar
  8. 8.
    Bergeron, S. E., Zhu, M., Thiem, S. M., Friderici, K. H., and Rubenstein, P. A. (2010) J. Biol. Chem., 285, 16087–16095.PubMedCrossRefGoogle Scholar
  9. 9.
    Dugina, V., Zwaenepoel, I., Gabbiani, G., Clement, S., and Chaponnier, C. (2009) J. Cell. Sci., 122, 2980–2988.PubMedCrossRefGoogle Scholar
  10. 10.
    Orban, J., Lorinczy, D., Nyitrai, M., and Hild, G. (2008) Biochem. Biophys. Res. Commun., 368, 696–702.PubMedCrossRefGoogle Scholar
  11. 11.
    Khaitlina, S., and Hinssen, H. (2008) Arch. Biochem. Biophys., 477, 279–284.PubMedCrossRefGoogle Scholar
  12. 12.
    Khaitlina, S. (2007) Tsitologiya, 49, 345–354.Google Scholar
  13. 13.
    Pokorna, E., Jordan, P. W., O’Neill, C. H., Zicha, D., Gilbert, C. S., and Vesely, P. (1994) Cell Motil. Cytoskeleton, 28, 25–33.PubMedCrossRefGoogle Scholar
  14. 14.
    Sahai, E., and Marshall, C. J. (2003) Nat. Cell Biol., 5, 711–719.PubMedCrossRefGoogle Scholar
  15. 15.
    Benedet, J. L., Bender, H., Jones, H., 3rd, Ngan, H. Y., and Pecorelli, S. (2000) Int. J. Gynaecol. Obstet., 70, 209–262.PubMedCrossRefGoogle Scholar
  16. 16.
    Wheelock, M. J., Soler, A. P., and Knudsen, K. A. (2001) J. Mammary Gland Biol. Neoplasia, 6, 275–285.PubMedCrossRefGoogle Scholar
  17. 17.
    Peinado, H., Olmeda, D., and Cano, A. (2007) Nat. Rev. Cancer, 7, 415–428.PubMedCrossRefGoogle Scholar
  18. 18.
    Bolos, V., Peinado, H., Perez-Moreno, M. A., Fraga, M. F., Esteller, M., and Cano, A. (2003) J. Cell Sci., 116, 499–511.PubMedCrossRefGoogle Scholar
  19. 19.
    Leung, C. T., and Brugge, J. S. (2012) Nature, 482, 410–413.PubMedCrossRefGoogle Scholar
  20. 20.
    Prasad, N. K., and Decker, S. J. (2005) J. Biol. Chem., 280, 13129–13136.PubMedCrossRefGoogle Scholar
  21. 21.
    Yamaguchi, H., and Condeelis, J. (2007) Biochim. Biophys. Acta, 1773, 642–652.PubMedCrossRefGoogle Scholar
  22. 22.
    Harborth, J., Elbashir, S. M., Bechert, K., Tuschl, T., and Weber, K. (2001) J. Cell. Sci., 114, 4557–4565.PubMedGoogle Scholar
  23. 23.
    Tondeleir, D., Lambrechts, A., Mueller, M., Jonckheere, V., Doll, T., Vandamme, D., Bakkali, K., Waterschoot, D., Lemaistre, M., Debeir, O., Decaestecker, C., Hinz, B., Staes, A., Timmerman, E., Colaert, N., Gevaert, K., Vandekerckhove, J., and Ampe, C. (2012) Mol. Cell Proteom., 11, 255–271.CrossRefGoogle Scholar
  24. 24.
    Vandekerckhove, J., Leavitt, J., Kakunaga, T., and Weber, K. (1980) Cell, 22, 893–899.PubMedCrossRefGoogle Scholar
  25. 25.
    Leavitt, J., Ng, S. Y., Varma, M., Latter, G., Burbeck, S., Gunning, P., and Kedes, L. (1987) Mol. Cell Biol., 7, 2467–2476.PubMedGoogle Scholar
  26. 26.
    Sadano, H., Taniguchi, S., Kakunaga, T., and Baba, T. (1988) J. Biol. Chem., 263, 15868–15871.PubMedGoogle Scholar
  27. 27.
    Dugina, V. B., Chipysheva, T. A., Ermilova, V. D., Gabbiani, D., Chaponnier, C., and Vasil’ev, Iu. M. (2008) Arkh. Patol., 70, 28–31.PubMedGoogle Scholar
  28. 28.
    Dugina, V. B., Ermilova, V. D., Chemeris, G. Iu., and Chipysheva, T. A. (2010) Arkh. Patol., 72, 12–15.PubMedGoogle Scholar
  29. 29.
    Condeelis, J., and Singer, R. H. (2005) Biol. Cell, 97, 97–110.PubMedCrossRefGoogle Scholar
  30. 30.
    Shum, M. S., Pasquier, E., Po’uha, S. T., O’Neill, G. M., Chaponnier, C., Gunning, P. W., and Kavallaris, M. (2011) FASEB J., 25, 4423–4433.PubMedCrossRefGoogle Scholar
  31. 31.
    Cannito, S., Novo, E., di Bonzo, L. V., Busletta, C., Colombatto, S., and Parola, M. (2010) Antioxid. Redox Signal., 12, 1383–1430.PubMedCrossRefGoogle Scholar
  32. 32.
    Takeichi, M. (1995) Curr. Opin. Cell Biol., 7, 619–627.PubMedCrossRefGoogle Scholar
  33. 33.
    Hirohashi, S. (1998) Am. J. Pathol., 153, 333–339.PubMedCrossRefGoogle Scholar
  34. 34.
    Berx, G., and van Roy, F. (2001) Breast Cancer Res., 3, 289–293.PubMedCrossRefGoogle Scholar
  35. 35.
    Van Aken, E., De Wever, O., Correia da Rocha, A. S., and Mareel, M. (2001) Virchows Arch., 439, 725–751.PubMedGoogle Scholar
  36. 36.
    Cavallaro, U., and Christofori, G. (2004) Nat. Rev. Cancer, 4, 118–132.PubMedCrossRefGoogle Scholar
  37. 37.
    Yoshiura, K., Kanai, Y., Ochiai, A., Shimoyama, Y., Sugimura, T., and Hirohashi, S. (1995) Proc. Natl. Acad. Sci. USA, 92, 7416–7419.PubMedCrossRefGoogle Scholar
  38. 38.
    Berx, G., Becker, K. F., Hofler, H., and van Roy, F. (1998) Hum. Mutat., 12, 226–237.PubMedCrossRefGoogle Scholar
  39. 39.
    Hajra, K. M., Ji, X., and Fearon, E. R. (1999) Oncogene, 18, 7274–7279.PubMedCrossRefGoogle Scholar
  40. 40.
    Tsao, S. W., Liu, Y., Wang, X., Yuen, P. W., Leung, S. Y., Yuen, S. T., Pan, J., Nicholls, J. M., Cheung, A. L., and Wong, Y. C. (2003) Eur. J. Cancer, 39, 524–531.PubMedCrossRefGoogle Scholar
  41. 41.
    Xiao, K., Oas, R. G., Chiasson, C. M., and Kowalczyk, A. P. (2007) Biochim. Biophys. Acta, 1773, 8–16.PubMedCrossRefGoogle Scholar
  42. 42.
    Nieman, M. T., Prudoff, R. S., Johnson, K. R., and Wheelock, M. J. (1999) J. Cell Biol., 147, 631–644.PubMedCrossRefGoogle Scholar
  43. 43.
    Tomita, K., van Bokhoven, A., van Leenders, G. J., Ruijter, E. T., Jansen, C. F., Bussemakers, M. J., and Schalken, J. A. (2000) Cancer Res., 60, 3650–3654.PubMedGoogle Scholar
  44. 44.
    Hazan, R. B., Phillips, G. R., Qiao, R. F., Norton, L., and Aaronson, S. A. (2000) J. Cell Biol., 148, 779–790.PubMedCrossRefGoogle Scholar
  45. 45.
    Li, G., Satyamoorthy, K., and Herlyn, M. (2001) Cancer Res., 61, 3819–3825.PubMedGoogle Scholar
  46. 46.
    Gravdal, K., Halvorsen, O. J., Haukaas, S. A., and Akslen, L. A. (2007) Clin. Cancer Res., 13, 7003–7011.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  • G. S. Shagieva
    • 1
  • L. V. Domnina
    • 1
  • T. A. Chipysheva
    • 2
  • V. D. Ermilova
    • 3
  • C. Chaponnier
    • 4
  • V. B. Dugina
    • 1
    Email author
  1. 1.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Institute of Carcinogenesis, Blokhin Cancer Research CenterRussian Academy of Medical SciencesMoscowRussia
  3. 3.Institute of Clinical Oncology, Blokhin Cancer Research CenterRussian Academy of Medical SciencesMoscowRussia
  4. 4.Dept of Pathology and Immunology, Faculty of MedicineUniversity of Geneva, CMUGenevaSwitzerland

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