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

Simvastatin inhibits the expression of stemness‑related genes and the metastatic invasion of human cancer cells via destruction of the cytoskeleton. Int J Oncol. 2017 Oct 13;: Authors: Tatè R, Zona E, De Cicco R, Trotta V, Urciuoli M, Morelli A, Baiano S, Carnuccio R, Fuggetta MP, Morelli F 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 act...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research