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Cell Biology and Toxicology

, Volume 26, Issue 6, pp 553–567 | Cite as

Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines

  • Modjtaba Emadi Baygi
  • Zahra Soheila Soheili
  • Ingo Schmitz
  • Shahram Sameie
  • Wolfgang A. Schulz
Article

Abstract

The epithelial–mesenchymal transition (EMT) is regarded as an important step in cancer metastasis. Snail, a master regulator of EMT, has been recently proposed to act additionally as a cell survival factor and inducer of motility. We have investigated the function of Snail (SNAI1) in prostate cancer cells by downregulating its expression via short (21-mer) interfering RNA (siRNA) and measuring the consequences on EMT markers, cell viability, death, cell cycle, senescence, attachment, and invasivity. Of eight carcinoma cell lines, the prostate carcinoma cell lines LNCaP and PC-3 showed the highest and moderate expression of SNAI1 mRNA, respectively, as measured by quantitative RT-PCR. Long-term knockdown of Snail induced a severe decline in cell numbers in LNCaP and PC-3 and caspase activity was accordingly enhanced in both cell lines. In addition, suppression of Snail expression induced senescence in LNCaP cells. SNAI1-siRNA-treated cells did not tolerate detachment from the extracellular matrix, probably due to downregulation of integrin α6. Expression of E-cadherin, vimentin, and fibronectin was also affected. Invasiveness of PC-3 cells was not significantly diminished by Snail knockdown. Our data suggest that Snail acts primarily as a survival factor and inhibitor of cellular senescence in prostate cancer cell lines. We therefore propose that Snail can act as early driver of prostate cancer progression.

Keywords

Cellular senescence Cell survival Integrin α6 Prostate cancer Snail 

Notes

Acknowledgments

We thank Dr. Parvaneh Nikpour and Christiane Hader for their assistance in some experiments and helpful suggestions and Dr. Volker Jung, Homburg, for providing the PC-3 daughter cell lines. This research was supported by National Institute of Genetic Engineering and Biotechnology through the grant no. 218. We also would like to acknowledge and extend our gratitude to Iranian Blood Transfusion Organization, especially Dr. Ali Talebian and Dr. Ahmad Gharabaghian, for their contribution to this study.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Modjtaba Emadi Baygi
    • 1
  • Zahra Soheila Soheili
    • 2
  • Ingo Schmitz
    • 3
    • 4
  • Shahram Sameie
    • 5
  • Wolfgang A. Schulz
    • 6
  1. 1.Department of Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
  2. 2.Department of BiochemistryNational Institute of Genetic Engineering and BiotechnologyTehranIran
  3. 3.Institute for Molecular and Clinical ImmunologyOtto-von-Guericke-UniversityMagdeburgGermany
  4. 4.Helmholtz Center for InfectionBraunschweigGermany
  5. 5.Iranian Blood Transfusion Research CenterTehranIran
  6. 6.Department of UrologyHeinrich Heine UniversityDüsseldorfGermany

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