PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma.
Biochem Biophys Res Commun
; 463(4): 839-45, 2015 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-26056003
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 PKCßI or ßII, 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.
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MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Carcinoma Hepatocelular
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NADPH Oxidases
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Proteína Quinase C-alfa
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Neoplasias Hepáticas
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article