ArticleProceedings of the National Academy of Sciences of the United States of America2014
Translation initiation factor eIF4F modifies the dexamethasone response in multiple myeloma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
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- Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy.Cell communication and signaling : CCS · 2024Review
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
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- Assessing eukaryotic initiation factor 4F subunit essentiality by CRISPR-induced gene ablation in the mouse.Cellular and molecular life sciences : CMLS · 2021Article
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- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
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- Eukaryotic Translation Initiation Factor 4AI: A Potential Novel Target in Neuroblastoma.Cells · 2021Article
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- A comparative study of small molecules targeting eIF4A.RNA (New York, N.Y.) · 2020Article
- Combined targeting of MEK and the glucocorticoid receptor for the treatment of RAS-mutant multiple myeloma.BMC cancer · 2020Article
- Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.Leukemia · 2020Article
- mRNA structural elements immediately upstream of the start codon dictate dependence upon eIF4A helicase activity.Genome biology · 2019Article
- eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5'UTR.Genome biology · 2019Article
- Amidino-Rocaglates: A Potent Class of eIF4A Inhibitors.Cell chemical biology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Enhanced protein synthesis capacity is associated with increased tumor cell survival, proliferation, and resistance to chemotherapy. Cancers like multiple myeloma (MM), which display elevated activity in key translation regulatory nodes, such as the PI3K/mammalian target of rapamycin and MYC-eukaryotic initiation factor (eIF) 4E pathways, are predicted to be particularly sensitive to therapeutic strategies that target this process. To identify novel vulnerabilities in MM, we undertook a focused RNAi screen in which components of the translation apparatus were targeted. Our screen was designed to identify synthetic lethal relationships between translation factors or regulators and dexamethasone (DEX), a corticosteroid used as frontline therapy in this disease. We find that suppression of all three subunits of the eIF4F cap-binding complex synergizes with DEX in MM to induce cell death. Using a suite of small molecules that target various activities of eIF4F, we observed that cell survival and DEX resistance are attenuated upon eIF4F inhibition in MM cell lines and primary human samples. Levels of MYC and myeloid cell leukemia 1, two known eIF4F-responsive transcripts and key survival factors in MM, were reduced upon eIF4F inhibition, and their independent suppression also synergized with DEX. Inhibition of eIF4F in MM exerts pleotropic effects unraveling a unique therapeutic opportunity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.