Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Taking aim at translation for tumor therapy
Bryan C. Barnhart, M. Celeste Simon
Bryan C. Barnhart, M. Celeste Simon
Published September 4, 2007
Citation Information: J Clin Invest. 2007;117(9):2385-2388. https://doi.org/10.1172/JCI33107.
View: Text | PDF
Commentary

Taking aim at translation for tumor therapy

  • Text
  • PDF
Abstract

Increased cap-dependent mRNA translation rates are frequently observed in human cancers. Mechanistically, many human tumors often overexpress the cap binding protein eukaryotic translation initiation factor 4E (eIF4E), leading to enhanced translation of numerous tumor-promoting genes. In this issue of the JCI, Graff and colleagues describe potent antitumor effects using second-generation antisense oligonucleotides for eIF4E (see the related article beginning on page 2638). If their results are recapitulated in a clinical setting, this strategy will provide a promising antitumor therapy with broad-reaching applications.

Authors

Bryan C. Barnhart, M. Celeste Simon

×

Figure 1

Mechanism of action of eIF4E ASOs.

Options: View larger image (or click on image) Download as PowerPoint
Mechanism of action of eIF4E ASOs.
(A) In normal tissues, eIF4E is typic...
(A) In normal tissues, eIF4E is typically sequestered by hypophosphorylated 4E-BPs, resulting in restricted translation rates. Homeostasis is maintained by limiting translation to essential genes, such as housekeeping genes. (B) In some tumors, oncogenic signaling results in primarily hyperphosphorylated 4E-BPs. Additionally, many tumors express high levels of eIF4E. Excess free eIF4E leads to increased translation rates, especially of genes involved in proliferation, survival, and metastasis. These increased translation rates help to drive tumor progression. (C) In tumors treated with eIF4E ASOs, eIF4E levels are significantly reduced. Despite 4E-BP hyperphosphorylation, reduced eIF4E levels inhibit translation rates, causing growth arrest or even apoptosis in tumors. It is likely that this strategy would have broad-reaching applications for tumors with eIF4E overexpression, oncogenic signaling (leading to 4E-BP hyperphosphorylation), or both. Since tumors frequently rely on increased translation for high proliferation rates and other malignant properties, reducing eIF4E levels should have a greater impact on them than it would on normal cells.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts