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

doi:10.18632/oncotarget.4483

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Research Papers:

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 and Che-Ming Teng

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Oncotarget. 2015; 6:24092-24104. https://doi.org/10.18632/oncotarget.4483

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Abstract

Min-Wu Chao1, Li-Ting Wang1, Chin-Yu Lai1, Xiao-Ming Yang2, Ya-Wen Cheng4, Kuo-Hsiung Lee2,3, Shiow-Lin Pan4,5,*, Che-Ming Teng1,*

1Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan

2Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

3Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan

4The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

5Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Shiow-Lin Pan, e-mail: [email protected]

Che-Ming Teng, e-mail: [email protected]

Keywords: colorectal cancer (CRC), eIF4E binding protein 1, hypoxia, prognosis, YXM110

Received: March 10, 2015 Accepted: June 19, 2015 Published: June 29, 2015

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 1α (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.

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Research Papers:

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

Abstract