title: eIF4E binding protein 1 expression is associated with clinical survival outcomes in colorectal cancer.
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.
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Wu
authors.initials: MW
authors.lastname: Chao
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Wang
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yang
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
authors.affiliation: Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shiow-Lin
authors.initials: SL
authors.lastname: Pan
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Teng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000470:Alkaloids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D018938:Caco-2 Cells; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D009369:Neoplasms / Q000378:metabolism; D010616:Phenanthrenes / Q000737:chemistry*; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D014176:Protein Biosynthesis; D054837:Quinolizidines / Q000737:chemistry*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000470:Alkaloids; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010616:Phenanthrenes; D010750:Phosphoproteins; D054837:Quinolizidines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000609610:YXM110; C007160:cryptopleurine
keywords: YXM110; colorectal cancer (CRC); eIF4E binding protein 1; hypoxia; prognosis