ArticleCancer discovery2015
Targeting Translation Initiation Bypasses Signaling Crosstalk Mechanisms That Maintain High MYC Levels in Colorectal Cancer.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 111 citations in OpenAlex.
- Unbiased profiling of translational landscape reveals TNFR2 as a translation-dependent vulnerability in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Non-gonadal PIWIL1/Aubergine drives regenerative and tumorigenic stem cell proliferation and tumorigenesis in the intestine.Cell reports · 2026Article
- LINC01963 promotes pancreatic ductal adenocarcinoma proliferation via METTL3/IGF2BP2 axis-mediated m⁶A modification of c-Myc.Journal of experimental & clinical cancer research : CR · 2026Article
- Silvestrol inhibits nasopharyngeal carcinoma cells and synergizes with CX-5461: Insights from a proteomics study.Molecular and clinical oncology · 2025Article
- VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization.Nature communications · 2025Article
- High expression of eIF4A1 promotes angiogenesis through the NF‑κB/VEGFA pathway and predicts poor prognosis in gastric cancer.Oncology reports · 2025Article
- Review
- Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology.Genes & diseases · 2025Review
- MYC upstream region orchestrates resistance to PI3K inhibitors in cancer cells through FOXO3a-mediated autophagic adaptation.Oncogene · 2024Article
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- Anti-tumor effects of the eIF4A inhibitor didesmethylrocaglamide and its derivatives in human and canine osteosarcomas.Scientific reports · 2024Article
- Anti-tumor Effects of the eIF4A Inhibitor Didesmethylrocaglamide and Its Derivatives in Human and Canine Osteosarcomas.Research square · 2024Article
- MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation.Nature communications · 2024Article
- The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.International journal of biological sciences · 2024Review
- Role of c-Myc in lung cancer: Progress, challenges, and prospects.Chinese medical journal pulmonary and critical care medicine · 2023Article
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options.Cells · 2023Review
- c-MYC mediates the crosstalk between breast cancer cells and tumor microenvironment.Cell communication and signaling : CCS · 2023Review
- Strategies to target the cancer driver MYC in tumor cells.Frontiers in oncology · 2023Review
- Significant position of C-myc in colorectal cancer: a promising therapeutic target.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledDeregulated expression of MYC is a driver of colorectal carcinogenesis, suggesting that inhibiting MYC may have significant therapeutic value. The PI3K and mTOR pathways control MYC turnover and translation, respectively, providing a rationale to target both pathways to inhibit MYC. Surprisingly, inhibition of PI3K does not promote MYC turnover in colon carcinoma cells, but enhances MYC expression because it promotes FOXO-dependent expression of growth factor receptors and MAPK-dependent transcription of MYC. Inhibition of mTOR fails to inhibit translation of MYC, because levels of 4EBPs are insufficient to fully sequester eIF4E and because an internal ribosomal entry site element in the 5'-untranslated region of the MYC mRNA permits translation independent of eIF4E. A small-molecule inhibitor of the translation factor eIF4A, silvestrol, bypasses the signaling feedbacks, reduces MYC translation, and inhibits tumor growth in a mouse model of colorectal tumorigenesis. We propose that targeting translation initiation is a promising strategy to limit MYC expression in colorectal tumors. SIGNIFICANCE: Inhibiting MYC function is likely to have a significant therapeutic impact in colorectal cancers. Here, we explore several strategies to target translation initiation in order to block MYC expression. We show that a small-molecule inhibitor of eIF4A inhibits MYC expression and suppresses tumor growth in vivo.
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Registered trials
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.