title: PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Shao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Peike
authors.initials: P
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Weicheng
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Science, Fudan University, Shanghai, PR China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Duan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China.
authors.forename: Shushu
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China. Electronic address: jiadongwei@fudan.edu.cn.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Jia
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China. Electronic address: yuanyuanruan@fudan.edu.cn.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, PR China; Institute of Biomedical Science, Fudan University, Shanghai, PR China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000074623:Dual Oxidases; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human; D051571:Protein Kinase C-alpha
keywords: DUOX2; Hepatocellular carcinoma; PKCα; Reactive oxygen species