Translation initiation factor eIF4F modifies the dexamethasone response in multiple myeloma
Open accessAbstract
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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Translation of MYC and BCL2 depends on eIF4A.
“Manual polysome fractionation experiments identified some eIF4A-dependent mRNAs such as MYC, BCL2, and MCL1 [22,23].”
From NRF2 Activation Confers Resistance to eIF4A Inhibitors in Cancer Therapy (2021) · cites this paper as [22]
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Necrotic Cells Alter IRE1α-XBP1 Signaling and Induce Transcriptional Changes in Glioblastoma
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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)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-09-02
- Volume
- 111
- Issue
- 37
- Pages
- 13421-13426
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4169926
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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