ArticleCell death & disease2020
Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 81 citations in OpenAlex.
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- Single-mRNA imaging and modeling reveal coupled translation initiation and elongation rates.eLife · 2026Article
- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
- Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.Nature communications · 2026Article
- Epithelial hypusination regulates Helicobacter pylori-induced gastric inflammation.Amino acids · 2026Article
- Ornithine decarboxylase influences granulosa cell proliferation and steroidogenesis: implications for ovarian regression in Wuding chickens.Frontiers in veterinary science · 2026Article
- Opposite effects of spermidine and GC7 in cell culture are dictated by distinct molecular targets.The Biochemical journal · 2025Article
- Inhibiting translation elongation by reducing eIF5A activity induces feedback inhibition of initiation, limiting tumour cell proliferation.Nature communications · 2025Article
- Protective role of epithelial deoxyhypusine synthase in colorectal carcinogenesis caused by deletion of the adenomatous polyposis coli gene.Cancer letters · 2025Article
- Polyamine metabolism in cancer: drivers of immune evasion, ferroptosis and therapy resistance.Expert reviews in molecular medicine · 2025Review
- Epithelial Hypusination Regulates Helicobacter pylori-induced Gastric Inflammation.Research square · 2025Article
- Mesenchymal stem cell extracellular vesicles ameliorate radiation-caused dry mouth via modulating immune balance and cell metabolism.Stem cell research & therapy · 2025Article
- Transcription factor FOS promotes ferroptosis and inflammation in S. aureus- infected osteomyelitis via EIF5A.Journal of orthopaedic surgery and research · 2025Article
- AZIN1-dependent polyamine synthesis accelerates tumor cell cycle progression and impairs effector T-cell function in osteosarcoma.Cell death & disease · 2025Article
- Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.Acta pharmaceutica Sinica. B · 2025Article
- Overcoming resistance to arginine deprivation therapy using GC7 in pleural mesothelioma.iScience · 2025Article
- Development of a reliable, sensitive, and convenient assay for the discovery of new eIF5A hypusination inhibitors.PloS one · 2025Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APC
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