Overexpression of eIF4F components in meningiomas and suppression of meningioma cell growth by inhibiting translation initiation.

Overexpression of eIF4F components in meningiomas and suppression of meningioma cell growth by inhibiting translation initiation.
Exp Neurol. 2017 Jun 10;:
Authors: Oblinger JL, Burns SS, Huang J, Pan L, Ren Y, Shen R, Douglas Kinghorn A, Bradley Welling D, Chang LS
Abstract
Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knockdown of these proteins strongly reduced cell proliferation. Among a series of 23 natural compounds evaluated, silvestrol, which inhibits eIF4A, was identified as being the most growth inhibitory in both primary meningioma and Ben-Men-1 cells. Silvestrol treatment of meningioma cells prominently induced G2/M arrest. Consistently, silvestrol significantly decreased the amounts of cyclins D1, E1, A, and B, PCNA and Aurora A. In addition, total and phosphorylated AKT, ERK and FAK, which have been shown to be important drivers for meningioma cell proliferation, were m...

Source: Experimental Neurology - June 10, 2017 Category: Neurology Authors: Oblinger JL, Burns SS, Huang J, Pan L, Ren Y, Shen R, Douglas Kinghorn A, Bradley Welling D, Chang LS Tags: Exp Neurol Source Type: research