Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and tumor progression without affecting normal growth

Annarita Miluzio, Anne Beugnet, Stefano Grosso, Daniela Brina, Marilena Mancino, Stefano Campaner, Bruno Amati, Ario de Marco, Stefano Biffo

Research output: Contribution to journalArticle

Abstract

Eukaryotic Initiation Factor 6 (eIF6) controls translation by regulating 80S subunit formation. eIF6 is overexpressed in tumors. Here, we demonstrate that eIF6 inactivation delays tumorigenesis and reduces tumor growth in vivo. eIF6+/- mice resist to Myc-induced lymphomagenesis and have prolonged tumor-free survival and reduced tumor growth. eIF6+/- mice are also protected by p53 loss. Myc-driven lymphomas contain PKCβII and phosphorylated eIF6; eIF6 is phosphorylated by tumor-derived PKCβII, but not by the eIF4F activator mTORC1. Mutation of PKCβII phosphosite of eIF6 reduces tumor growth. Thus, eIF6 is a rate-limiting controller of initiation of translation, able to affect tumorigenesis and tumor growth. Modulation of eIF6 activity, independent from eIF4F complex, may lead to a therapeutical avenue in tumor therapy.

Original languageEnglish
Pages (from-to)765-775
Number of pages11
JournalCancer Cell
Volume19
Issue number6
DOIs
Publication statusPublished - Jun 14 2011

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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  • Cite this

    Miluzio, A., Beugnet, A., Grosso, S., Brina, D., Mancino, M., Campaner, S., Amati, B., de Marco, A., & Biffo, S. (2011). Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and tumor progression without affecting normal growth. Cancer Cell, 19(6), 765-775. https://doi.org/10.1016/j.ccr.2011.04.018