title: Notch1 promotes hepatitis B virus X protein-induced hepatocarcinogenesis via Wnt/β-catenin pathway.
abstract: Hepatitis B virus X protein (HBx) is implicated in the pathogenesis of hepatocellular carcinoma (HCC) via a network of signaling pathways. Notch pathway is a major member of the network. Notch signaling may generate opposing effect in different steps of carcinogenesis, depending on the tumor cell type and the status of other signaling pathways, such as Wnt signaling pathway. Our previous studies have shown that activated Notch1 signaling is required for HBx to promote proliferation and survival of human hepatic cell line L02. However, the exact mechanisms remain vague. Here, we used L02/HBx cell lines as a cell model to study the relationship between Notch and Wnt/β-catenin pathways in promoting proliferation. We observed that activated Notch1 and Wnt/β-catenin signaling pathways and L02 cell malignant transformation were induced by HBx. Inhibition of the Notch1 pathway decreased the activation of Wnt/β-catenin pathway and cell proliferation, while inhibition of the Wnt/β-catenin pathway impaired cell proliferation, but did not significantly affect Notch1 signaling pathway in L02/HBx cells. Furthermore, inhibition of the Wnt/β-catenin pathway overcame the inhibition effect of knockdown Notch1 on proliferation and survival in L02/HBx cells. Additionally, the activity of Wnt/β-catenin signaling appears to be consistent with Fzd10 expression. Therefore, we demonstrate that Wnt signaling is downstream of the Notch pathway in regulating proliferation of L02/HBx cells, and which may be related to Fzd10 instead of Fzd7. These data suggest a new model of HBx-related HCC via cooperation between Wnt and Notch pathways.
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Si
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006515:Hepatitis B virus / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D060449:Wnt Signaling Pathway
chemical_list: C121168:FZD10 protein, human; D051157:Frizzled Receptors; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein