ArticleJournal of experimental & clinical cancer research : CR2019
Eukaryotic initiation factor 4A2 promotes experimental metastasis and oxaliplatin resistance in colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 70 citations in OpenAlex.
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- Patient-derived xenograft models in cancer therapy: technologies and applications.Signal transduction and targeted therapy · 2023Review
- Patient-derived xenograft model in colorectal cancer basic and translational research.Animal models and experimental medicine · 2023Review
- eIF4A1 Is a Prognostic Marker and Actionable Target in Human Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Role and therapeutic potential of DEAD-box RNA helicase family in colorectal cancer.Frontiers in oncology · 2023Review
- Translational regulation of cell invasion through extracellular matrix-an emerging role for ribosomes.F1000Research · 2023Review
- Single-cell RNA analysis to identify five cytokines signaling in immune-related genes for melanoma survival prognosis.Frontiers in immunology · 2023Article
- Article
- Copy number variation of EIF4A2 loci related to phenotypic traits in Chinese cattle.Veterinary medicine and science · 2022Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDeregulation of protein translation control is a hallmark of cancers. Eukaryotic initiation factor 4A2 (EIF4A2) is required for mRNA binding to ribosome and plays an important role in translation initiation. However, little is known about its functions in colorectal cancer (CRC).
methodsAnalysis of CRC transcriptome data from TCGA identified that EIF4A2 was associated with poor prognosis. Immunohistochemistry study of EIF4A2 was carried out in 297 paired colorectal tumor and adjacent normal tissue samples. In vitro and in vivo cell-biological assays were performed to study the biological functions of EIF4A2 on experimental metastasis and sensitivity to oxaliplatin treatment. Bioinformatic prediction, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay were carried out to unveil the transcription factor of EIF4A2 regulation.
resultsEIF4A2 Expression is significantly higher in colorectal tumors. Multivariate analysis suggests EIF4A2 as an independent predictor of overall, disease-free and progression-free survival. Dysfunction of EIF4A2 by genetic knock-down or small-molecule inhibitor silvestrol dramatically inhibited CRC invasion and migration, sphere formation and enhanced sensitivity to oxaliplatin treatment in vitro and in vivo. Notably, EIF4A2 knock-down also suppressed lung metastasis in vivo. qRT-PCR and immunoblotting analyses identified c-Myc as a downstream target and effector of EIF4A2. ChIP and dual-luciferase reporter assays validated the bioinformatical prediction of ZNF143 as a specific transcription factor of EIF4A2.
conclusionsEIF4A2 promotes experimental metastasis and oxaliplatin resistance in CRC. Silvestrol inhibits tumor growth and has synergistic effects with oxaliplatin to induce apoptosis in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models.
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