Author
Listed:
- Shensi Shen
(Gustave Roussy Cancer Campus)
- Sara Faouzi
(Gustave Roussy Cancer Campus
Université Paris-Sud, Université Paris-Saclay)
- Amandine Bastide
(University Montpellier)
- Sylvain Martineau
(Institut Curie, PSL Research University, CNRS UMR3348
Université Paris Sud, Université Paris-Saclay, CNRS UMR3348
Equipe Labellisée Ligue Nationale Contre le Cancer)
- Hélène Malka-Mahieu
(Institut Curie, PSL Research University, CNRS UMR3348
Université Paris Sud, Université Paris-Saclay, CNRS UMR3348
Equipe Labellisée Ligue Nationale Contre le Cancer)
- Yu Fu
(Gustave Roussy Cancer Campus
Université Paris-Sud, Université Paris-Saclay)
- Xiaoxiao Sun
(University of California)
- Christine Mateus
(Gustave Roussy Cancer Campus)
- Emilie Routier
(Gustave Roussy Cancer Campus)
- Severine Roy
(Gustave Roussy Cancer Campus)
- Laurent Desaubry
(CNRS-Strasbourg University)
- Fabrice André
(Gustave Roussy Cancer Campus
Université Paris-Sud, Université Paris-Saclay)
- Alexander Eggermont
(Université Paris-Sud, Université Paris-Saclay)
- Alexandre David
(University Montpellier)
- Jean-Yves Scoazec
(Université Paris-Sud, Université Paris-Saclay)
- Stéphan Vagner
(Institut Curie, PSL Research University, CNRS UMR3348
Université Paris Sud, Université Paris-Saclay, CNRS UMR3348
Equipe Labellisée Ligue Nationale Contre le Cancer
Gustave Roussy Cancer Campus)
- Caroline Robert
(Gustave Roussy Cancer Campus
Université Paris-Sud, Université Paris-Saclay
Gustave Roussy Cancer Campus)
Abstract
Cancer persister cells tolerate anticancer drugs and serve as the founders of acquired resistance and cancer relapse. Here we show that a subpopulation of BRAFV600 mutant melanoma cells that tolerates exposure to BRAF and MEK inhibitors undergoes a reversible remodelling of mRNA translation that evolves in parallel with drug sensitivity. Although this process is associated with a global reduction in protein synthesis, a subset of mRNAs undergoes an increased efficiency in translation. Inhibiting the eIF4A RNA helicase, a component of the eIF4F translation initiation complex, abrogates this selectively increased translation and is lethal to persister cells. Translation remodelling in persister cells coincides with an increased N6-methyladenosine modification in the 5′-untranslated region of some highly translated mRNAs. Combination of eIF4A inhibitor with BRAF and MEK inhibitors effectively inhibits the emergence of persister cells and may represent a new therapeutic strategy to prevent acquired drug resistance.
Suggested Citation
Shensi Shen & Sara Faouzi & Amandine Bastide & Sylvain Martineau & Hélène Malka-Mahieu & Yu Fu & Xiaoxiao Sun & Christine Mateus & Emilie Routier & Severine Roy & Laurent Desaubry & Fabrice André & Al, 2019.
"An epitranscriptomic mechanism underlies selective mRNA translation remodelling in melanoma persister cells,"
Nature Communications, Nature, vol. 10(1), pages 1-14, December.
Handle:
RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13360-6
DOI: 10.1038/s41467-019-13360-6
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