ArticleCancer cell international2021
Targeted intervention of eIF4A1 inhibits EMT and metastasis of pancreatic cancer cells via c-MYC/miR-9 signaling.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Survivin mRNA lipid nanoparticles and CTLA-4 inhibitor co-delivery activates anti-tumor cytotoxic T-lymphocytes for oral cancer immunotherapy.Medical oncology (Northwood, London, England) · 2026Article
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- C-MYC as a key effector of WNT, PI3K/AKT, MAPK, and TGF-β signaling pathways in regulation of epithelial-mesenchymal transition during tumor metastasis.Cancer cell international · 2026Review
- Proteomic characterization of intrahepatic cholangiocarcinoma identifies risk-stratifying subgroups and EIF4A1 as a therapeutic target.Nature communications · 2026Article
- Combined HDAC and eIF4A inhibition: A novel epigenetic therapy for pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2026Article
- eIF4A1 exacerbates myocardial ischemia-reperfusion injury in mice by promoting nuclear translocation of transgelin/p53.Acta pharmacologica Sinica · 2025Article
- Curcumin Inhibits the Development of Pancreatic Cancer by Targeting the circ_0079440/miR-522-3p/EIF4A1 Pathway.Cell biochemistry and biophysics · 2025Article
- Rocaglamide Suppresses Allergic Reactions by Regulating IL-4 Receptor Signaling.Molecules (Basel, Switzerland) · 2025Article
- MK2-mediated AKT/MYC signaling activation promotes epithelial-mesenchymal transition in lung adenocarcinoma.Frontiers in genetics · 2025Article
- Article
- Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Tumor-associated characteristics and immune dysregulation in nasopharyngeal carcinoma under the regulation of m7G-related tumor microenvironment cells.World journal of surgical oncology · 2024Article
- MicroRNAs as the critical regulators of epithelial mesenchymal transition in pancreatic tumor cells.Heliyon · 2024Review
- Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance.Cancer metastasis reviews · 2024Review
- Integrative analysis of spatial and single-cell transcriptome data from human pancreatic cancer reveals an intermediate cancer cell population associated with poor prognosis.Genome medicine · 2024Article
- Metastasis-Related Signature for Clinically Predicting Prognosis and Tumor Immune Microenvironment of Osteosarcoma Patients.Molecular biotechnology · 2023Article
- Network analysis reveals miRNA crosstalk between periodontitis and oral squamous cell carcinoma.BMC oral health · 2023Article
- Eukaryotic translation initiation factor 4A1 in the pathogenesis and treatment of cancers.Frontiers in molecular biosciences · 2023Review
- Targeting KRAS in PDAC: A New Way to Cure It?Cancers · 2022Review
- Novel eIF4A1 inhibitors with anti-tumor activity in lymphoma.Molecular medicine (Cambridge, Mass.) · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOwing to the lack of effective treatment options, early metastasis remains the major cause of pancreatic ductal adenocarcinoma (PDAC) recurrence and mortality. However, the molecular mechanism of early metastasis is largely unknown. We characterized the function of eukaryotic translation initiation factors (eIFs) in epithelial-mesenchymal-transition (EMT) and metastasis in pancreatic cancer cells to investigate whether eIFs and downstream c-MYC affect EMT and metastasis by joint interference.
methodsWe used The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to analyze eIF4A1 expression in PDAC tissues and further validated the findings with a microarray containing 53 PDAC samples. Expression regulation and pharmacological inhibition of eIF4A1 and c-MYC were performed to determine their role in migration, invasion, and metastasis in pancreatic cancer cells in vitro and in vivo.
resultsElevated eIF4A1 expression was positively correlated with lymph node infiltration, tumor size, and indicated a poor prognosis. eIF4A1 decreased E-cadherin expression through the c-MYC/miR-9 axis. Loss of eIF4A1 and c-MYC decreased the EMT and metastasis capabilities of pancreatic cancer cells, whereas upregulation of eIF4A1 attenuated the inhibition of EMT and metastasis induced by c-MYC downregulation. Treatment with the eIF4A1 inhibitor rocaglamide (RocA) or the c-MYC inhibitor Mycro3 either alone or in combination significantly decreased the expression level of EMT markers in pancreatic cancer cells in vitro. However, the efficiency and safety of RocA alone were not inferior to those of the combination treatment in vivo.
conclusionOverexpression of eIF4A1 downregulated E-cadherin expression through the c-MYC/miR-9 axis, which promoted EMT and metastasis of pancreatic cancer cells. Despite the potential feedback loop between eIF4A1 and c-MYC, RocA monotherapy is a promising treatment inhibiting eIF4A1-induced PDAC metastasis.
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