ArticleCell death & disease2015
The malignant phenotype in breast cancer is driven by eIF4A1-mediated changes in the translational landscape.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 170 citations in OpenAlex.
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Compartment-Specific CD138 Expression Defines an Aggressive Breast Cancer Phenotype with Distinct Transcriptomic Features.Cancers · 2026Article
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
- Peptide antibody tools to dissect specific functions of eIF4A paralogs in cancer.Discover oncology · 2025Article
- Epigenetic alterations facilitate transcriptional and translational programs in hypoxia.Nature cell biology · 2025Article
- High expression of eIF4A1 promotes angiogenesis through the NF‑κB/VEGFA pathway and predicts poor prognosis in gastric cancer.Oncology reports · 2025Article
- Dynamics and Regulation of mRNA Cap Recognition by Human eIF4F.bioRxiv : the preprint server for biology · 2025Article
- eIF4A1 exacerbates myocardial ischemia-reperfusion injury in mice by promoting nuclear translocation of transgelin/p53.Acta pharmacologica Sinica · 2025Article
- eIF4F-mediated dysregulation of mRNA translation in cancer.RNA (New York, N.Y.) · 2025Review
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- The DEAD-box RNA helicase eIF4A is a crucial factor for stem-cell activity and reproduction of the parasiteFrontiers in cellular and infection microbiology · 2025Article
- Eukaryotic initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs.Nucleic acids research · 2024Article
- Exploiting Translation Machinery for Cancer Therapy: Translation Factors as Promising Targets.International journal of molecular sciences · 2024Review
- Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study.Scientific reports · 2024Article
- Cell reprogramming design by transfer learning of functional transcriptional networks.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- A second-generation eIF4A RNA helicase inhibitor exploits translational reprogramming as a vulnerability in triple-negative breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- IGF2BP2 Drives Cell Cycle Progression in Triple-Negative Breast Cancer by Recruiting EIF4A1 to Promote the m6A-Modified CDK6 Translation Initiation Process.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A.eLife · 2023Article
- 5'-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I.Frontiers of medicine · 2023Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
Abstract
Human mRNA DeXD/H-box helicases are ubiquitous molecular motors that are required for the majority of cellular processes that involve RNA metabolism. One of the most abundant is eIF4A, which is required during the initiation phase of protein synthesis to unwind regions of highly structured mRNA that would otherwise impede the scanning ribosome. Dysregulation of protein synthesis is associated with tumorigenesis, but little is known about the detailed relationships between RNA helicase function and the malignant phenotype in solid malignancies. Therefore, immunohistochemical analysis was performed on over 3000 breast tumors to investigate the relationship among expression of eIF4A1, the helicase-modulating proteins eIF4B, eIF4E and PDCD4, and clinical outcome. We found eIF4A1, eIF4B and eIF4E to be independent predictors of poor outcome in ER-negative disease, while in contrast, the eIF4A1 inhibitor PDCD4 was related to improved outcome in ER-positive breast cancer. Consistent with these data, modulation of eIF4A1, eIF4B and PCDC4 expression in cultured MCF7 cells all restricted breast cancer cell growth and cycling. The eIF4A1-dependent translatome of MCF7 cells was defined by polysome profiling, and was shown to be highly enriched for several classes of oncogenic genes, including G-protein constituents, cyclins and protein kinases, and for mRNAs with G/C-rich 5'UTRs with potential to form G-quadruplexes and with 3'UTRs containing microRNA target sites. Overall, our data show that dysregulation of mRNA unwinding contributes to the malignant phenotype in breast cancer via preferential translation of a class of genes involved in pro-oncogenic signaling at numerous levels. Furthermore, immunohistochemical tests are promising biomarkers for tumors sensitive to anti-helicase therapies.
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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.