Expression and activity of eIF6 trigger Malignant Pleural Mesothelioma growth in vivo

Miluzio, A, Oliveto, S, Pesce, E, Mutti, L, Murer, B, Grosso, S, Ricciardi, S, Brina, D and Biffo, S 2015, 'Expression and activity of eIF6 trigger Malignant Pleural Mesothelioma growth in vivo' , Oncotarget, 2015 (6) , pp. 37471-37485.

PDF - Published Version
Available under License Creative Commons Attribution.

Download (11MB) | Preview


eIF6 is an antiassociation factor that regulates the availability of active 80S. Its activation is driven by the RACK1/PKCβ axis, in a mTORc1 independent manner. We previously described that eIF6 haploinsufficiency causes a striking survival in the Eμ-Myc mouse lymphoma model, with lifespans extended up to 18 months. Here we screen for eIF6 expression in human cancers. We show that Malignant Pleural Mesothelioma tumors (MPM) and a MPM cell line (REN cells) contain high levels of hyperphosphorylated eIF6. Enzastaurin is a PKC beta inhibitor used in clinical trials. We prove that Enzastaurin treatment decreases eIF6 phosphorylation rate, but not eIF6 protein stability. The growth of REN, in vivo, and metastasis are reduced by either Enzastaurin treatment or eIF6 shRNA. Molecular analysis reveals that eIF6 manipulation affects the metabolic status of malignant mesothelioma cells. Less glycolysis and less ATP content are evident in REN cells depleted for eIF6 or treated with Enzastaurin (Anti-Warburg effect). We propose that eIF6 is necessary for malignant mesothelioma growth, in vivo, and can be targeted by kinase inhibitors.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: Oncotarget
Publisher: Impact Journals
ISSN: 1949-2553
Depositing User: USIR Admin
Date Deposited: 08 Nov 2016 11:53
Last Modified: 15 Feb 2022 21:23

Actions (login required)

Edit record (repository staff only) Edit record (repository staff only)


Downloads per month over past year