PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan; Duan, Fangfang; Zhang, Mingming; Song, Shushu; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

doi:10.1016/j.bbrc.2015.06.021

Cited by 15 publications

(10 citation statements)

References 33 publications

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“…It has been reported that PKC β isoenzyme is responsible for the activation/phosphorylation of p66/shc, which can bind to cytochrome c and stimulate the generation of ROS [ 149 ]. Recent findings have demonstrated that PKC α plays a critical role in hepatocarcinoma development by inducing DUOX (a member family of NOX) expression and ROS production [ 150 ]. Moreover, also PKC δ has been shown to be implicated in NOX activation that via alterations of redox state influence retinoic acid-induced differentiation of neuroblastoma cells [ 151 ].…”

Section: Redox-signaling Pathways Involved In Tumorigenesis and Inmentioning

confidence: 99%

Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

Marengo

Nitti

Furfaro

et al. 2016

Oxidative Medicine and Cellular Longevity

251

174

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Reactive oxygen species (ROS) and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy.

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Section: Redox-signaling Pathways Involved In Tumorigenesis and Inmentioning

confidence: 99%

Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

Marengo

Nitti

Furfaro

et al. 2016

Oxidative Medicine and Cellular Longevity

251

174

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“…Overexpression of DUOX2 and DUOX2-dependent ROS generation in HCC has been attributed to post-transcriptional upregulation of DUOX2 by protein kinase C alpha (PKCα), which is also commonly overexpressed in HCC and associated with poor prognosis[160]. Observations of DUOX2 overexpression in pancreatic cancer are thought to be linked to pancreatitis and associated pro-inflammatory cytokines, and studies in pancreatic cancer cell lines indeed confirm induction of DUOX2 in response to bacterial lipopolysaccharide (LPS) or the inflammatory cytokine IFN-γ, due to concerted actions of transcription factors STAT1 and NF-κB [108, 161].…”

Section: Mechanisms Of Duox Regulationmentioning

confidence: 99%

Paradoxical roles of dual oxidases in cancer biology

Little

Sulovari

Danyal

et al. 2017

Free Radical Biology and Medicine

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Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities.

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“…In HCC cell lines, DUOX2 expression and activity seem to be positively regulated by protein kinase C alpha (PKCa), which is overexpressed in HCC and is implicated in malignant transformation through enhancing multiple cellular signaling pathways. Silencing of DUOX2 abrogated PKCa-induced ROS generation, as well as AKT/MAPK activation and cell proliferation, migration, and invasion, suggesting that the interplay between PKCa and DUOX2 can be involved in HCC development (Wang et al, 2015).…”

Section: Duoxs and Cancermentioning

confidence: 97%

The role of dual oxidases in physiology and cancer

Faria

Fortunato

2020

Genet. Mol. Biol.

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NOX/DUOX enzymes are transmembrane proteins that carry electrons through biological membranes generating reactive oxygen species. The NOX family is composed of seven members, which are NOX1 to NOX5 and DUOX1 and 2. DUOX enzymes were initially called thyroid oxidases, based on their high expression level in the thyroid tissue. However, DUOX expression has been documented in several extrathyroid tissues, mostly at the apical membrane of the salivary glands, the airways, and the intestinal tract, revealing additional cellular functions associated with DUOX-related H 2 O 2 generation. In this review, we will briefly summarize the current knowledge regarding DUOX structure and physiological functions, as well as their possible role in cancer biology.

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PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

Cited by 15 publications

References 33 publications

Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

Paradoxical roles of dual oxidases in cancer biology

The role of dual oxidases in physiology and cancer

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