ArticleLaboratory investigation; a journal of technical methods and pathology2016
Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted via translation initiation factors eIF4E and eIF4GI.
Article in Laboratory investigation; a journal of technical methods and pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Discovery of a small-molecule inhibitor of eIF4E suppressing tumor proliferation via lipid metabolic reprogramming.Journal of advanced research · 2026Article
- Multipurpose RNA maturation factors dysregulate multiple mRNA processing steps simultaneously and provide new therapeutic opportunities.RNA biology · 2025Review
- Differentially expressed profiles of LncRNAs in pterygium.BMC ophthalmology · 2025Article
- Unveiling the unexplored novel signatures for osteoporosis via a detailed bioinformatics and molecular experiments based approach.American journal of translational research · 2024Article
- The eukaryotic translation initiation factor eIF4E unexpectedly acts in splicing thereby coupling mRNA processing with translation: eIF4E induces widescale splicing reprogramming providing system-wide connectivity between splicing, nuclear mRNA export and translation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- Cancer cells hijack RNA processing to rewrite the message.Biochemical Society transactions · 2022Article
- Mild hyperthermia induced by gold nanorods acts as a dual-edge blade in the fate of SH-SY5Y cells via autophagy.Scientific reports · 2021Article
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- Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products.Molecules (Basel, Switzerland) · 2021Review
- All-trans retinoic acid reverses malignant biological behavior of hepatocarcinoma cells by regulating miR-200 family members.Genes & diseases · 2021Article
- Role of EIF4G1 network in non-small cell lung cancers (NSCLC) cell survival and disease progression.Journal of cellular and molecular medicine · 2021Article
- MTA2 promotes the metastasis of esophageal squamous cell carcinoma via EIF4E-Twist feedback loop.Cancer science · 2021Article
- Tumor-Derived Exosomal eIF4E as a Biomarker for Survival Prediction in Patients with Non-Small Cell Lung Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- The role of olefin geometry in the activity of hydrocarbon stapled peptides targeting eukaryotic translation initiation factor 4E (eIF4E).Organic & biomolecular chemistry · 2019Article
- Paip1 overexpression is involved in the progression of gastric cancer and predicts shorter survival of diagnosed patients.OncoTargets and therapy · 2019Article
- Eukaryotic Translation Initiation Factor 4 Gamma 1 (EIF4G1): a target for cancer therapeutic intervention?Cancer cell international · 2019Article
- The effect of mesenchymal stem cells' secretome on lung cancer progression is contingent on their origin: primary or metastatic niche.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) is upregulated during Prostate cancer progression and modulates cell growth and metastasis.Scientific reports · 2018Article
- Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL.Nature communications · 2018Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis underlies cancer morbidity and accounts for disease progression and significant death rates generally and in non-small cell lung cancer (NSCLC) particularly. Therefore, it is critically important to understand the molecular events that regulate metastasis. Accumulating data portray a central role for protein synthesis, particularly translation initiation (TI) factors eIF4E and eIF4G in tumorigenesis and patients' survival. We have published that eIF4E/eIF4GI activities and consequently NSCLC cell migration are modulated by bone-marrow mesenchymal stem cell secretomes, suggesting a role for TI in metastasis. Here, we aimed to expand our understanding of the TI factors significance to NSCLC characteristics, particularly epithelial-to-mesenchymal transition (EMT) and migration, supportive of metastasis. In a model of NSCLC cell lines (H1299, H460), we inhibited eIF4E/eIF4GI's expressions (siRNA, ribavirin) and assessed NSCLC cell lines' migration (scratch), differentiation (EMT, immunoblotting), and expression of select microRNAs (qPCR). Initially, we determined an overexpression of several TI factors (eIF4E, eIF4GI, eIF4B, and DHX29) and their respective targets in NSCLC compared with normal lung samples (70-350%↑, P<0.05). Knockdown (KD) of eIF4E/eIF4GI in NSCLC cell lines (70%↓, P<0.05) also manifested in decreased target levels (ERα, SMAD5, NFkB, CyclinD1, c-MYC, and HIF1α) (20-50%↓, P<0.05). eIF4E/eIF4GI KD also attenuated cell migration (60-75%↓, P<0.05), EMT promoters (15-90%↓, P<0.05), and enhanced EMT suppressors (30-380%↑, P<0.05). The importance of eIF4E KD to NSCLC phenotype was further corroborated with its inhibitor, ribavirin. Changes in expression of essential microRNAs implicated in NSCLC cell migration concluded the study (20-100%, P<0.05). In summary, targeting eIF4E/eIF4GI reduces migration and EMT, both essential for metastasis, thereby underscoring the potential of TI targeting in NSCLC therapy, especially the already clinically employed agents (ribavirin/4EGI). Comparison of these findings with previously reported effects of eIF4E/eIF4GI KD in multiple myeloma suggests a collective role for these TI factors in cancer progression.
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