Cited by 64Multiple Myeloma Research and TreatmentsRNA and protein synthesis mechanismsPI3K/AKT/mTOR signaling in cancer

Translation initiation factor eIF4F modifies the dexamethasone response in multiple myeloma

Open access
Robert, Francis, Roman, William, Bramoullé, Alexandre, Fellmann, Christof, Roulston, Anne, Shustik, Chaim, Porco, John A., Shore, Gordon C. +2 more·2014·Proceedings of the National Academy of Sciences

Abstract

Significance: Multiple myeloma (MM) is a cancer that develops in the bone marrow and remains incurable to this day. It is a cancer type that shows hallmarks of deregulated protein synthesis control. To uncover new vulnerabilities in this disease, we performed a focused RNAi screen to identify components of the translation apparatus that, when depleted, would sensitize tumor cells to dexamethasone (DEX), a component of frontline therapy in this cancer. We found that suppression of eukaryotic initiation factor 4F, a heterotrimeric complex required for cap-dependent translation initiation, is a modifier of the DEX response in MM. Our efforts uncover a previously unidentified vulnerability in MM that should be explored clinically.

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Crossref · 10.1073/pnas.1402650111

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37 of 37 references verified0 citation errors · 0 not checkable

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Authors
Robert, F., Roman, W., Bramoullé, A., Fellmann, C., Roulston, A., Shustik, C., Porco, J. A., Shore, G. C., Sebag, M., & Pelletier, J.
Affiliations
  • Departments of aBiochemistry,
  • Medicine and Hematology, and
  • McGill University (CA)
  • Mirimus, Inc., Cold Spring Harbor, NY 11724; and
  • Boston University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2014-09-02
Volume
111
Issue
37
Pages
13421-13426
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2024968250
Cited by
64
References
37
Citations by year
2026: 4 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 1 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 10 · 2017: 3 · 2016: 8 · 2015: 3
FWCI
3.31
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canadian Institutes of Health Research (106530_1, 123503_1)
  • National Institute of General Medical Sciences (GM-073855, R01GM073855)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
eIF4F, multiple myeloma, dexamethasone, translation initiation, synthetic lethality, eIF4E, c-Myc, Mcl-1, PI3K/mTOR pathway, steroid resistance, RNAi screen, cell death
MeSH terms
Benzofurans, Dexamethasone, Humans, Multiple Myeloma, Suppression, Genetic, Triterpenes, Proto-Oncogene Proteins c-myc, Cell Death, RNA Interference, Eukaryotic Initiation Factor-4F, Cell Line, Tumor, Molecular Targeted Therapy, Genes, Modifier, Myeloid Cell Leukemia Sequence 1 Protein

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