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Virtanen SS, Ishizu T, Sandholm JA, et al. Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells. Oncotarget. 2018;9(66):32593-32608doi: 10.18632/oncotarget.25961.
Virtanen, S. S., Ishizu, T., Sandholm, J. A., Löyttyniemi, E., Väänänen, H. K., Tuomela, J. M., & Härkönen, P. L. (2018). Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells. Oncotarget, 9(66), 32593-32608. https://doi.org/10.18632/oncotarget.25961
Virtanen, Sanna S, et al. "Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells." Oncotarget vol. 9,66 (2018): 32593-32608. doi: https://doi.org/10.18632/oncotarget.25961
Virtanen SS, Ishizu T, Sandholm JA, Löyttyniemi E, Väänänen HK, Tuomela JM, Härkönen PL. Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells. Oncotarget. 2018 Aug 24;9(66):32593-32608. doi: 10.18632/oncotarget.25961. eCollection 2018 Aug 24. PMID: 30220968; PMCID: PMC6135693.
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Oncotarget. 2018 Aug 24;9(66):32593-32608. doi: 10.18632/oncotarget.25961. eCollection 2018 Aug 24.

Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells.

Oncotarget

Sanna S Virtanen, Tamiko Ishizu, Jouko A Sandholm, Eliisa Löyttyniemi, H Kalervo Väänänen, Johanna M Tuomela, Pirkko L Härkönen

Affiliations

  1. University of Turku, Institute of Biomedicine, FI-20520 Turku, Finland.
  2. Turku University of Applied Sciences, Health and Well-being, FI-20520 Turku, Finland.
  3. Cell Imaging Core, Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20521 Turku, Finland.
  4. University of Turku, Department of Biostatistics, FI-20520 Turku, Finland.

PMID: 30220968 PMCID: PMC6135693 DOI: 10.18632/oncotarget.25961

Abstract

Bisphosphonates are used for prevention of osteoporosis and metastatic bone diseases. Anti-invasive effects on various cancer cells have also been reported, but the mechanisms involved are not well-understood. We investigated the effects of the nitrogen-containing bisphosphonate alendronate (ALN) on the regulation of actin cytoskeleton in PC-3 cells. We analyzed the ALN effect on the organization and the dynamics of actin, and on the cytoskeleton-related regulatory proteins cofilin, p21-associated kinase 2 (PAK2), paxillin and focal adhesion kinase. Immunostainings of cofilin in ALN-treated PC-3 cells and xenografts were performed, and the role of cofilin in ALN-regulated F-actin organization and migration/invasion in PC-3 cells was analyzed using cofilin knockdown and transfection. We demonstrate that disrupted F-actin organization and decreased cell motility in ALN-treated PC-3 cells were associated with decreased levels of total and phosphorylated cofilin. PAK2 levels were also lowered but adhesion-related proteins were not altered. The knockdown of cofilin similarly impaired F-actin organization and decreased invasion of PC-3 cells, whereas in the cells transfected with a cofilin expressing vector, ALN treatment did not decrease cellular cofilin levels and migration as in mock transfected cells. ALN also reduced immunohistochemical staining of cofilin in PC-3 xenografts. Our results suggest that reduction of cofilin has an important role in ALN-induced disruption of the actin cytoskeleton and inhibition of the PC-3 cell motility and invasion. These data also support the idea that the nitrogen-containing bisphosphonates could be efficacious in inhibition of prostate cancer invasion and metastasis, if delivered in a pharmacological formulation accessible to the tumors.

Keywords: actin cytoskeleton; bisphosphonate; cofilin; invasion; prostate cancer

Conflict of interest statement

CONFLICTS OF INTEREST There are no competing interests for any of the authors.

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