Notch2 is a crucial regulator of self-renewal and tumorigenicity in human hepatocellular carcinoma cells
| Autor: | Chao Liu, Xiang-De Shi, Cao Yi, Wen-Rui Wu, Rui Zhang, Lei-Bo Xu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system Cancer Research Pathology medicine.medical_specialty Carcinoma Hepatocellular endocrine system diseases Carcinogenesis Cell Down-Regulation Mice Nude Biology medicine.disease_cause Mice 03 medical and health sciences Downregulation and upregulation Cell Line Tumor Biomarkers Tumor medicine Animals Humans CD90 Receptor Notch2 RNA Small Interfering neoplasms Cell Proliferation Cell growth Cell Cycle Liver Neoplasms Hep G2 Cells General Medicine Cell cycle digestive system diseases Up-Regulation 030104 developmental biology medicine.anatomical_structure Oncology Drug Resistance Neoplasm Cell culture Neoplastic Stem Cells Cancer research Female RNA Interference Fluorouracil Stem cell |
| Zdroj: | Oncology Reports. 36:181-188 |
| ISSN: | 1791-2431 1021-335X |
| Popis: | The Notch pathway plays an important role in both stem cell biology and cancer. Notch2 was reported to be upregulated in human hepatocellular carcinoma (HCC) tissues. However, the biological function of Notch2 in human HCC cells has not yet been documented. The aim of this study was to investigate its possible function on the progression of human HCC cells. The expression of Notch2 was detected in four human HCC cell lines by western blotting. Next, Notch2 was knocked down by small interference RNA (siRNA) in human HCC cells. The role of Notch2 in human HCC cells was investigated by cell proliferation assay, colony formation assay, chemoresistance and xenograft formation assay. In the present study, western blotting revealed that the expression of Notch2 was upregulated in human HCC cell lines. Genetic depletion of Notch2 in HCC cells not only resulted in significantly inhibited proliferation, cell cycle progression and colony formation ability but also increased its sensitivity to 5-fluorouracil (5-FU) compared with controls. In addition, upregulation of Notch2 was discovered in CD90 positive HCC cells, CD90 is a marker of hepatic stem cells. Most importantly, knockdown of Notch2 in HCC cells impaired the tumor formation in vivo. Taken together, our findings indicate that Notch2 may confer stemness properties in HCC; downregulation of Notch2 inhibited the proliferation and tumor formation of HCC cells and increase their sensitivity to 5-FU, suggesting Notch2 as a potential therapeutic target for HCC. |
| Databáze: | OpenAIRE |
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