{"doi":"10.1002/cac2.12011","title":"Role of <i>eIF4E</i> on epithelial‐mesenchymal transition, invasion, and chemoresistance of prostate cancer cells","abstract":"Dear Editor, Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death for men in the United States [1]. PCa with similar Gleason score has been reported to show substantial interpatient heterogeneity and differential prostate cancer-specific mortality rate [2]. Such heterogeneity in PCa often results in different therapeutic responses among patients, including therapy resistance, therapeutic failure, relapse, and metastasis [3]. Numerous oncogenes, such as eukaryotic translation initiation factor 4E (eIF4E), have been reported to be involved in epithelial-mesenchymal transition (EMT) and/or drug resistance in PCa [4]. We previously demonstrated that eIF4E overexpression was involved in chemoresistance of triple-negative breast cancer and silencing eIF4E significantly inhibited cancer cell proliferation and sensitized cancer cells to chemotherapy in a patient-derived xenograft mouse model [5]. In addition, eIF4E phosphorylation is known to stimulate the translation of matrix metalloproteinase 3 (MMP3) and Snail mRNAs to promote EMT in PCa [6]. Furthermore, the complexity and dynamic nature of EMT contributes to the heterogeneity of aggressive cancer cells [7]. The precise role of eIF4E in EMT, invasion, and chemoresistance in PCa is still to be established with consideration of different subpopulations in order to develop precision medicine for PCa. In this work, we aimed to explore the role of eIF4E in EMT, invasion, and chemoresistance in PCa for establishing a promising new therapeutic strategy by regulating eIF4E expression using (1-aminoethyl)iminobis[N-oleicylcysteinyl-1-aminoethyl) propionamide] (ECO)/small interfering RNA (siRNA) nanoparticles previously developed in our lab [8-10] for PCa therapy in the context of tumor heterogeneity. Two PCa cell lines (PC3 and DU145) and their corresponding paclitaxel (PTX)-resistant cell lines (PC3-DR and DU145-DR) were investigated to assess the role of eIF4E in EMT, invasion, and chemoresistance of PCa cells (more details in Supplementary information). The average IC50 of PTX for PC3-DR cells (577.88 nmol/L) was about 69 times higher than that for PC3 cells (8.37 nmol/L), and the average IC50 of PTX for DU145-DR cells (379.15 nmol/L) was about 85 times higher than that for DU145 cells (4.44 nmol/L), indicating that both the drug-resistant cell lines acquired significant resistance to PTX treatment. Interestingly, PC3-DR and DU145-DR cells displayed different morphology and invasiveness from their corresponding parental cell lines (Figure 1A-D). PC3 cells were inherently invasive and displayed spindle-like mesenchymal morphology, while PC3-DR cells exhibited a squamous or epithelial morphology (Figure 1A and B). In addition, wound healing and transwell invasion assays revealed that PC3-DR cells were less migratory and invasive than PC3 cells (Figure 1C and D, Supplementary Fig. S1). On the contrary, DU145 cells displayed the epithelial hallmark of densely packed squamous morphology, whereas DU145-DR cells exhibited an elongated and spindle-like morphology, which is characteristic of mesenchymal cells (Figure 1A and B). DU145-DR cells were more invasive than DU145 cells, as evidenced by an increase in migrated cells in transwell migration assay and narrower gap in wound healing assay at 24 h (Figure 1C and D, Supplementary Fig. S1).Moreover,significant down-regulation of mesenchymal markers, such as N-cadherin and ZEB-1, was observed in PC3-DR cells as compared to PC3 cells. On the other hand, significant up-regulation of N-cadherin, vimentin, and ZEB-1 was observed in DU145-DR cells as compared to DU145 cells (Figure 1E and F). Taken together, these results demonstrated that although both PC3-DR and DU145-DR cells developed significant chemoresistance to PTX, only DU145-DR cells acquired features of EMT, characteriing by the transition to mesenchymal phenotype and increased invasion in response to PTX resistance. For the inherently mesenchymal PC3 ce","journal":"Cancer Communications","year":2020,"id":109948,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":365445,"name":"Amita Vaidya","orcid":null,"position":1,"is_corresponding":false},{"id":523966,"name":"Da Sun","orcid":"0000-0003-4170-1981","position":2,"is_corresponding":false},{"id":523967,"name":"Yan Zhang","orcid":"0000-0002-8105-7644","position":3,"is_corresponding":false},{"id":365444,"name":"Nadia Ayat","orcid":null,"position":4,"is_corresponding":false},{"id":523968,"name":"Andrew L. Schilb","orcid":"0000-0002-7344-5671","position":5,"is_corresponding":false},{"id":364020,"name":"Zheng‐Rong Lu","orcid":"0000-0001-8185-9519","position":6,"is_corresponding":false},{"id":362146,"name":"Xujie Liu","orcid":"0000-0001-8713-4287","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-18T23:12:54.309019Z","pmid":"32189455","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}