title: Notch2 is a crucial regulator of self-renewal and tumorigenicity in human hepatocellular carcinoma cells.
abstract: 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.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Pancreato-Biliary Surgery, SunYat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Wen-Rui
authors.initials: WR
authors.lastname: Wu
authors.affiliation: SunYat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: SunYat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Xiang-De
authors.initials: XD
authors.lastname: Shi
authors.affiliation: Department of Emergency, SunYat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Cao
authors.initials: C
authors.lastname: Yi
authors.affiliation: SunYat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Lei-Bo
authors.initials: LB
authors.lastname: Xu
authors.affiliation: SunYat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D051883:Receptor, Notch2 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C497764:NOTCH2 protein, human; D034741:RNA, Small Interfering; D051883:Receptor, Notch2; D005472:Fluorouracil