eIF4E binding protein 1 expression is associated with clinical survival outcomes in colorectal cancer

Min Wu Chao, Li Ting Wang, Chin Yu Lai, Xiao Ming Yang, Ya Wen Cheng, Kuo Hsiung Lee, Shiow Lin Pan, Che Ming Teng

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

eIF4E binding protein 1 (4E-BP1), is critical for cap-dependent and cap-independent translation. This study is the first to demonstrate that 4E-BP1 expression correlates with colorectal cancer (CRC) progression. Compared to its expression in normal colon epithelial cells, 4E-BP1 was upregulated in CRC cell lines and was detected in patient tumor tissues. Furthermore, high 4E-BP1 expression was statistically associated with poor prognosis. Hypoxia has been considered as an obstacle for cancer therapeutics. Our previous data showed that YXM110, a cryptopleurine derivative, exhibited anticancer activity via 4E-BP1 depletion. Here, we investigated whether YXM110 could inhibit protein synthesis under hypoxia. 4E-BP1 expression was notably decreased by YXM110 under hypoxic conditions, implying that cap-independent translation could be suppressed by YXM110. Moreover, YXM110 repressed hypoxia-inducible factor 1a (HIF- 1α) expression, which resulted in decreased downstream vascular endothelial growth factor (VEGF) expression. These observations highlight 4E-BP1 as a useful biomarker and therapeutic target, indicating that YXM110 could be a potent CRC therapeutic drug.

Original languageEnglish
Pages (from-to)24092-24104
Number of pages13
JournalOncotarget
Volume6
Issue number27
DOIs
Publication statusPublished - 2015

Keywords

  • Colorectal cancer (CRC)
  • EIF4E binding protein 1
  • Hypoxia
  • Prognosis
  • YXM110

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Chao, M. W., Wang, L. T., Lai, C. Y., Yang, X. M., Cheng, Y. W., Lee, K. H., Pan, S. L., & Teng, C. M. (2015). eIF4E binding protein 1 expression is associated with clinical survival outcomes in colorectal cancer. Oncotarget, 6(27), 24092-24104. https://doi.org/10.18632/oncotarget.4483