Inhibition of Hes1 enhances lapatinib sensitivity in gastric cancer sphere-forming cells
| Autor: | Donglin Wang, Huiwen Ma, Lulu Wang, Dairong Li, Weiqi Nian, Yan Li, Zhijuan Wu, Huiqing Yu, Luchun Li, Jianghe Shao |
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| Rok vydání: | 2017 |
| Předmět: |
cancer stem cells
0301 basic medicine Homeobox protein NANOG Cancer Research Cellular differentiation epithelial-mesenchymal transition Notch signaling pathway epidermal growth factor receptor-tyrosine kinase inhibitor neurogenic locus notch homolog protein 1 Biology Lapatinib 03 medical and health sciences 0302 clinical medicine Cancer stem cell Neurogenic Locus Notch Homolog Protein 1 medicine HES1 gastric cancer Articles 030104 developmental biology Oncology 030220 oncology & carcinogenesis embryonic structures Cancer cell Cancer research medicine.drug |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| DOI: | 10.3892/ol.2017.6683 |
| Popis: | It has been considered that the neurogenic locus notch homolog protein (Notch) signaling pathway serves an essential role in cellular differentiation, proliferation and apoptosis. However, the function of the Notch signaling pathway in gastric cancer stem cells (GCSCs) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity remains unclear. The present study aimed to delineate the role of the Notch1 signaling pathway in GCSCs and lapatinib sensitivity. Sphere-forming cells were separated from human gastric cancer MKN45 parental cells. The sphere-forming cells exhibited characteristics of CSCs and higher Notch1 expression compared with that of parental cells. To investigate the role of the Notch1 signaling pathway in GCSCs, the expression of transcription factor Hes1 (Hes1) was knocked down using small interfering RNA against Hes1. It was observed that Hes1 expression was significantly downregulated in knocked down cells. The inhibition of Hes1 suppressed the properties of CSCs, as indicated by significant decreases in the expression of the transcription factor sex determining region Y-box 2, epithelial cell adhesion molecule and the homeobox protein Nanog and reduced spheroid colony formation. In addition, epithelial-mesenchymal transition was significantly impaired in sphere-forming cells following Hes1 knockdown. Furthermore, the inhibition of Hes1 effectively enhanced lapatinib sensitivity in sphere-forming cells. These results suggest that sphere-forming gastric cancer cells possess the characteristics of CSCs, and that the Notch1 signaling pathway serves an essential role in the maintenance of CSCs and lapatinib sensitivity. |
| Databáze: | OpenAIRE |
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