Cited by 376RNA and protein synthesis mechanismsPI3K/AKT/mTOR signaling in cancerRNA modifications and cancer

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Targeting the eIF4F Translation Initiation Complex: A Critical Nexus for Cancer Development

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Pelletier, Jerry, Graff, Jeremy, Ruggero, Davide, Sonenberg, Nahum·2015·Cancer Research

DOI 10.1158/0008-5472.can-14-2789PMC PMC4299928

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Abstract

Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA–ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. Cancer Res; 75(2); 250–63. ©2014 AACR.

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BindingDB Entry 50010656: Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase.
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BindingDB Entry 50009066: Consideration of Binding Kinetics in the Design of Stapled Peptide Mimics of the Disordered Proteins Eukaryotic Translation Initiation Factor 4E-Binding Protein 1 and Eukaryotic Translation Initiation Factor 4G.
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BindingDB Entry 50018671: Discovery of an eIF4A Inhibitor with a Novel Mechanism of Action.
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BindingDB (2020) · UC San Diego · doi:10.7270/q20004p7
BindingDB Entry 50013394: A cell-penetrant lactam-stapled peptide for targeting eIF4E protein-protein interactions.
BindingDB (2022) · UC San Diego · doi:10.7270/q2ks6w8f
BindingDB Entry 50000895: Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition.
BindingDB (2020) · UC San Diego · doi:10.7270/q2nc63ps

Authors: Pelletier, J., Graff, J., Ruggero, D., & Sonenberg, N.
Affiliations: Institut du cancer Rosalind & Morris Goodman (CA)
Eli Lilly (United States) (US)
University of California, San Francisco (US)
Corresponding author: Pelletier, Jerry
ORCID: Pelletier, Jerry
Ruggero, Davide
Sonenberg, Nahum
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2015-01-14
Volume: 75
Issue: 2
Pages: 250-263
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-14-2789
PMC: PMC4299928
OpenAlex: W2005176113
Cited by: 367
References: 227
Citations by year: 2026: 18 · 2025: 18 · 2024: 30 · 2023: 36 · 2022: 30 · 2021: 39 · 2020: 32 · 2019: 35 · 2018: 40 · 2017: 33 · 2016: 37 · 2015: 19
FWCI: 4.17
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship@McGill (McGill) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: U.S. Public Health Service (MOP-106530, MOP-115126)
National Cancer Institute (R01CA140456, R01CA184624, R01CA154916)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords: eIF4F, translation initiation, cancer, translational regulation, oncogenic signaling, Ras, c-Myc, metastasis, epithelial-mesenchymal transition, angiogenesis, cell proliferation
MeSH terms: Animals, Antineoplastic Agents, Humans, Neoplasms, Eukaryotic Initiation Factor-4F, Molecular Targeted Therapy

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Targeting the eIF4F Translation Initiation Complex: A Critical Nexus for Cancer Development

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