ArticleCancer research2014
A hypusine-eIF5A-PEAK1 switch regulates the pathogenesis of pancreatic cancer.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 97 citations in OpenAlex.
- Trial
- Lipid Nanoparticle Co-Delivery of mRNA and a Small Molecule Drug for Oral Cancer Chemoimmunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Article
- Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.Nature communications · 2026Article
- Single-cell sequencing reveals the functional heterogeneity of melanoma cells and their crosstalk with the tumor microenvironment.Frontiers in genetics · 2026Article
- Lipid nanoparticle co-delivery of mRNA and a small molecule drug for oral cancer chemoimmunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Current understanding of PEAK family members in regulation of cellular signaling pathways and cancer therapy.Molecular and cellular biochemistry · 2025Review
- Prognostic, oncogenic roles, and pharmacogenomic features of AMD1 in hepatocellular carcinoma.Cancer cell international · 2024Article
- Colorectal carcinoma progression is not influenced by the pseudokinase PEAK1.Scientific reports · 2024Article
- Article
- ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity.Cell reports · 2024Article
- Targeting PEAK1 sensitizes anaplastic thyroid carcinoma cells harboring BRAFHistology and histopathology · 2024Article
- 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
- RNA: The Unsuspected Conductor in the Orchestra of Macromolecular Crowding.Chemical reviews · 2024Review
- SUMOylation modulates eIF5A activities in both yeast and pancreatic ductal adenocarcinoma cells.Cellular & molecular biology letters · 2024Article
- Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification.Gastroenterology · 2023Article
- Targeted inhibition of eIF5ACell death & disease · 2023Article
- The Polyamine-Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma.Blood cancer discovery · 2023Article
- PEAK1 Y635 phosphorylation regulates cell migration through association with Tensin3 and integrins.The Journal of cell biology · 2022Article
- A transcriptomic signature for prostate cancer relapse prediction identified from the differentially expressed genes between TP53 mutant and wild-type tumors.Scientific reports · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Deregulation of protein synthesis is a hallmark of cancer cell proliferation, survival, and metastatic progression. eIF5A1 and its highly related isoform eIF5A2 are translation initiation factors that have been implicated in a range of human malignancies, but how they control cancer development and disease progression is still poorly understood. Here, we investigated how eIF5A proteins regulate pancreatic ductal adenocarcinoma (PDAC) pathogenesis. eIF5A proteins are the only known proteins regulated by a distinct posttranslational modification termed hypusination, which is catalyzed by two enzymes, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). The highly selective nature of the hypusine modification and its amenability to pharmacologic inhibition make eIF5A proteins attractive therapeutic targets. We found that the expression and hypusination of eIF5A proteins are upregulated in human PDAC tissues and in premalignant pancreatic intraepithelial neoplasia tissues isolated from Pdx-1-Cre: LSL-KRAS(G12D) mice. Knockdown of eIF5A proteins in PDAC cells inhibited their growth in vitro and orthotopic tumor growth in vivo, whereas amplification of eIF5A proteins increased PDAC cell growth and tumor formation in mice. Small-molecule inhibitors of DHPS and DOHH both suppressed eIF5A hypusination, preventing PDAC cell growth. Interestingly, we found that eIF5A proteins regulate PDAC cell growth by modulating the expression of PEAK1, a nonreceptor tyrosine kinase essential for PDAC cell growth and therapy resistance. Our findings suggest that eIF5A proteins utilize PEAK1 as a downstream effector to drive PDAC pathogenesis and that pharmacologic inhibition of the eIF5A-hypusine-PEAK1 axis may provide a novel therapeutic strategy to combat this deadly disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.