CHE-MING TENG2018-09-102018-09-102015http://www.scopus.com/inward/record.url?eid=2-s2.0-84943423433&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/392044eIF4E 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.Colorectal cancer (CRC); EIF4E binding protein 1; Hypoxia; Prognosis; YXM110[SDGs]SDG3eIF4E binding protein 1; hypoxia inducible factor 1alpha; luciferase; natural product; unclassified drug; vasculotropin; yxm110; alkaloid; antineoplastic agent; cryptopleurine; EIF4EBP1 protein, human; HIF1A protein, human; hypoxia inducible factor 1alpha; phenanthrene derivative; phosphoprotein; quinolizidine derivative; signal transducing adaptor protein; vasculotropin A; VEGFA protein, human; YXM110; aged; Article; cancer staging; cap independent translation; colorectal cancer; controlled study; correlation analysis; disease course; DNA structure; down regulation; female; genetic transcription and translation; human; human cell; human tissue; hypoxia; hypoxia responsive element; major clinical study; male; protein expression; protein synthesis inhibition; recurrent disease; RNA translation; survival time; upregulation; Caco-2 cell line; chemistry; Colorectal Neoplasms; gene expression regulation; HCT 116 cell line; immunohistochemistry; metabolism; mortality; neoplasm; prognosis; protein synthesis; treatment outcome; tumor cell line; Adaptor Proteins, Signal Transducing; Alkaloids; Antineoplastic Agents; Caco-2 Cells; Cell Line, Tumor; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Neoplasms; Phenanthrenes; Phosphoproteins; Prognosis; Protein Biosynthesis; Quinolizidines; Treatment Outcome; Vascular Endothelial Growth Factor Ajournal article10.18632/oncotarget.4483