ArticleThe Journal of biological chemistry2015
Eukaryotic Translation Initiation Factor 5A (EIF5A) Regulates Pancreatic Cancer Metastasis by Modulating RhoA and Rho-associated Kinase (ROCK) Protein Expression Levels.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
- Single-cell sequencing reveals the functional heterogeneity of melanoma cells and their crosstalk with the tumor microenvironment.Frontiers in genetics · 2026Article
- eIF5A maintains intestinal epithelial homeostasis by sustaining intestinal stem cells.Cell regeneration (London, England) · 2025Article
- MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.Signal transduction and targeted therapy · 2024Review
- The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.International journal of molecular sciences · 2024Review
- Construction of a nomogram for predicting HNSCC distant metastasis and identification of EIF5A as a hub gene.Scientific reports · 2024Article
- SUMOylation modulates eIF5A activities in both yeast and pancreatic ductal adenocarcinoma cells.Cellular & molecular biology letters · 2024Article
- Targeted inhibition of eIF5ACell death & disease · 2023Article
- Inhibiting eukaryotic initiation factor 5A (eIF5A) hypusination attenuated activation of the SIK2 (salt-inducible kinase 2)-p4E-BP1 pathway involved in ovarian cancer cell proliferation and migration.Molecular biology reports · 2023Article
- Comparison of Human Eukaryotic Translation Initiation Factors 5A1 and 5AL1: Identification of Amino Acid Residues Important for EIF5A1 Lysine 50 Hypusination and Its Protein Stability.International journal of molecular sciences · 2023Article
- Eukaryotic initiation factor 6 regulates mechanical responses in endothelial cells.The Journal of cell biology · 2022Article
- Role of eIF5A in Mitochondrial Function.International journal of molecular sciences · 2022Review
- Aggressive Natural Killer Cell Leukemia in an Adolescent Patient: A Case Report and Literature Review.Frontiers in pediatrics · 2022Article
- MiR-1301-3p Inhibits Epithelial-Mesenchymal Transition via Targeting RhoA in Pancreatic Cancer.Journal of oncology · 2022Article
- Review
- EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway.Cell & bioscience · 2021Article
- Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine.Nature communications · 2021Article
- What determines eukaryotic translation elongation: recent molecular and quantitative analyses of protein synthesis.Open biology · 2020Review
- Clinical significance of eukaryotic translation initiation factor 5A2 in papillary thyroid cancer.Bioengineered · 2020Article
- Tumor Microenvironment Remodeling Enables Bypass of Oncogenic KRAS Dependency in Pancreatic Cancer.Cancer discovery · 2020Article
- Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes.International journal of molecular sciences · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with an overall survival rate of less than 5%. The poor patient outcome in PDAC is largely due to the high prevalence of systemic metastasis at the time of diagnosis and lack of effective therapeutics that target disseminated cells. The fact that the underlying mechanisms driving PDAC cell migration and dissemination are poorly understood have hindered drug development and compounded the lack of clinical success in this disease. Recent evidence indicates that mutational activation of K-Ras up-regulates eIF5A, a component of the cellular translational machinery that is critical for PDAC progression. However, the role of eIF5A in PDAC cell migration and metastasis has not been investigated. We report here that pharmacological inhibition or genetic knockdown of eIF5A reduces PDAC cell migration, invasion, and metastasis in vitro and in vivo. Proteomic profiling and bioinformatic analyses revealed that eIF5A controls an integrated network of cytoskeleton-regulatory proteins involved in cell migration. Functional interrogation of this network uncovered a critical RhoA/ROCK signaling node that operates downstream of eIF5A in invasive PDAC cells. Importantly, eIF5A mediates PDAC cell migration and invasion by modulating RhoA/ROCK protein expression levels. Together our findings implicate eIF5A as a cytoskeletal rheostat controlling RhoA/ROCK protein expression during PDAC cell migration and metastasis. Our findings also implicate the eIF5A/RhoA/ROCK module as a potential new therapeutic target to treat metastatic PDAC cells.
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