The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas.

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The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas.

Oncotarget. 2016 Nov 08;7(45):72415-72430

Authors: D'Andrea A, Gritti I, Nicoli P, Giorgio M, Doni M, Conti A, Bianchi V, Casoli L, Sabò A, Mironov A, Beznoussenko GV, Amati B

Abstract
The oncogenic transcription factor Myc is required for the progression and maintenance of diverse tumors. This has led to the concept that Myc itself, Myc-activated gene products, or associated biological processes might constitute prime targets for cancer therapy. Here, we present an in vivo reverse-genetic screen targeting a set of 241 Myc-activated mRNAs in mouse B-cell lymphomas, unraveling a critical role for the mitochondrial ribosomal protein (MRP) Ptcd3 in tumor maintenance. Other MRP-coding genes were also up regulated in Myc-induced lymphoma, pointing to a coordinate activation of the mitochondrial translation machinery. Inhibition of mitochondrial translation with the antibiotic Tigecycline was synthetic-lethal with Myc activation, impaired respiratory activity and tumor cell survival in vitro, and significantly extended lifespan in lymphoma-bearing mice. We have thus identified a novel Myc-induced metabolic dependency that can be targeted by common antibiotics, opening new therapeutic perspectives in Myc-overexpressing tumors.

PMID: 27635472 [PubMed - indexed for MEDLINE]

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