title: Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway.
abstract: The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.
authors.affiliation: Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei, Taiwan.|Department of Chemical Engineering & Materials Science, Yuan-Ze University, Taoyuan, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: M T
authors.initials: MT
authors.lastname: Weng
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: P N
authors.initials: PN
authors.lastname: Tsao
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: H L
authors.initials: HL
authors.lastname: Lin
authors.affiliation: Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: C C
authors.initials: CC
authors.lastname: Tung
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: M C
authors.initials: MC
authors.lastname: Change
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Y T
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: J M
authors.initials: JM
authors.lastname: Wong
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: S C
authors.initials: SC
authors.lastname: Wei
mesh_terms: D016922:Cellular Senescence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000072056:Transcription Factor HES-1 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14