Simvastatin inhibits the expression of stemness‑related genes and the metastatic invasion of human cancer cells via destruction of the cytoskeleton

  • Authors:
    • Rosarita Tatè
    • Enrica Zona
    • Rosanna De Cicco
    • Veronica Trotta
    • Maria Urciuoli
    • Alessandro Morelli
    • Salvatore Baiano
    • Rosa Carnuccio
    • Maria Pia Fuggetta
    • Franco Morelli
  • View Affiliations

  • Published online on: October 13, 2017     https://doi.org/10.3892/ijo.2017.4158
  • Pages:1851-1859
0

Abstract

Statins are a class of drugs that inhibit the rate-limiting steps in the cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the farnesylation and geranylgeranylation of several functional proteins, such as RhoA and other small guanosine triphosphate-binding proteins, that are important in maintaining the undifferentiated status of the cells. In the present study, we hypothesized that simvastatin, likely through the inhibition of farnesylation and geranylgeranylation of Rac1, Cd42 and RhoA, induces a destruction/restructuration of the cytoskeleton that decreases mechanical strain transfer to the nuclei, inducing the loss of transmission of regulatory signals from the cytoskeleton to the nucleoskeleton. Although this remains at present a hypothesis and is not easy to define if the de-structuration of the cytoskeleton is a secondary effect of simvastatin treatment or the inhibition of post-translational protein modification have a precise role in the structuration of actin cytoskeleton, we speculate that these signal variations could inhibit the expression of certain stemness genes, which could therefore be considered nucleoskeleton-associated and mechanically regulated genes. On the other hand, the restructuration of the cytoskeleton inhibits the formation of lamellipodia and filopodia, which likely decreases the capability of cancer cells to invade the extracellular matrix, thereby modulating the equilibrium between proliferation, differentiation and metastatic invasion in human cancer cells. On the basis of our results we think that simvastatin, alone or in combination with conventional drugs, may have a possible role in cancer therapy.

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December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
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APA
Tatè, R., Zona, E., De Cicco, R., Trotta, V., Urciuoli, M., Morelli, A. ... Morelli, F. (2017). Simvastatin inhibits the expression of stemness‑related genes and the metastatic invasion of human cancer cells via destruction of the cytoskeleton. International Journal of Oncology, 51, 1851-1859. https://doi.org/10.3892/ijo.2017.4158
MLA
Tatè, R., Zona, E., De Cicco, R., Trotta, V., Urciuoli, M., Morelli, A., Baiano, S., Carnuccio, R., Fuggetta, M. P., Morelli, F."Simvastatin inhibits the expression of stemness‑related genes and the metastatic invasion of human cancer cells via destruction of the cytoskeleton". International Journal of Oncology 51.6 (2017): 1851-1859.
Chicago
Tatè, R., Zona, E., De Cicco, R., Trotta, V., Urciuoli, M., Morelli, A., Baiano, S., Carnuccio, R., Fuggetta, M. P., Morelli, F."Simvastatin inhibits the expression of stemness‑related genes and the metastatic invasion of human cancer cells via destruction of the cytoskeleton". International Journal of Oncology 51, no. 6 (2017): 1851-1859. https://doi.org/10.3892/ijo.2017.4158