Hydrogen peroxide promotes transformation of rat liver non‐neoplastic epithelial cells through activation of epidermal growth factor receptor

Huang, Ruo‐Pan; Ao, Ping; Golard, A.; Hossain, Moharmmad Z.; Huang, Ruochun; Liu, Yaguang; Boynton, Alton L.

doi:10.1002/mc.1030

Cited by 72 publications

(53 citation statements)

References 39 publications

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“…faecalis induces cell proliferation through hydrogen peroxide-mediated EGFR activation. Several studies indicate that exposure to oxidative stress, such as the presence of H 2 O 2 , preferentially facilitates EGFR activation (38,58,59), enhances cell proliferation (43,57,70), and thereby promotes tumorigenesis (29). Because E. faecalis can generate a considerable amount of oxidants, such as superoxide and H 2 O 2 (30), our next series of experiments was designed to determine whether H 2 O 2 production by E. faecalis VF could induce cell proliferation via EGFR activation.…”

Section: High Frequency Of E Faecalis Infection In Oral Tumorsmentioning

confidence: 99%

Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation

et al. 2012

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f Enterococcus faecalis is a member of the intestinal and oral microbiota that may affect the etiology of colorectal and oral cancers. The mechanisms by which E. faecalis may contribute to the initiation and progression of these cancers remain uncertain. Epidermal growth factor receptor (EGFR) signaling is postulated to play a crucial role in oral carcinogenesis. A link between E. faecalis and EGFR signaling in oral cancer has not been elucidated. The present study aimed to evaluate the association between E. faecalis and oral cancer and to determine the underlying mechanisms that link E. faecalis to EGFR signaling. We report the high frequency of E. faecalis infection in oral tumors and the clinical association with EGFR activation. Using human oral cancer cells, we support the clinical findings and demonstrate that E. faecalis can induce EGFR activation and cell proliferation. E. faecalis activates EGFR through production of H 2 O 2 , a signaling molecule that activates several signaling pathways. Inhibitors of H 2 O 2 (catalase) and EGFR (gefitinib) significantly blocked E. faecalis-induced EGFR activation and cell proliferation. Therefore, E. faecalis infection of oral tumor tissues suggests a possible association between E. faecalis infection and oral carcinogenesis. Interaction of E. faecalis with host cells and production of H 2 O 2 increase EGFR activation, thereby contributing to cell proliferation.

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Section: High Frequency Of E Faecalis Infection In Oral Tumorsmentioning

confidence: 99%

Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation

et al. 2012

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“…This results in prolonged downstream activation of proliferative molecules such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) (9), and the lack of receptor turnover has been shown to mediate tumor promotion in non-neoplastic rat liver epithelial cells (10). To gain more insight into H 2 O 2 -induced EGFR signaling and hyperplastic responses, we examined the trafficking of the receptor under oxidative stress.…”

Section: Activation Of the Epidermal Growth Factor (Egf)mentioning

confidence: 99%

Epidermal Growth Factor Receptor Exposed to Oxidative Stress Undergoes Src- and Caveolin-1-dependent Perinuclear Trafficking

Khan

Heidinger

Levy

et al. 2006

Journal of Biological Chemistry

150

161

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The epidermal growth factor (EGF) receptor (EGFR) has been found to be overexpressed in several types of cancer cells, and the regulation of its oncogenic potential has been widely studied. The paradigm for EGFR down-regulation involves the trafficking of activated receptor molecules from the plasma membrane, through clathrin-coated pits, and into the cell for lysosomal degradation. We have previously shown that oxidative stress generated by H 2 O 2 results in aberrant phosphorylation of the EGFR. This leads to the loss of c-Cbl-mediated ubiquitination of the EGFR and, consequently, prevents its degradation. However, we have found that c-Cbl-mediated ubiquitination is required solely for degradation but not for internalization of the EGFR under oxidative stress. To further examine the fate of the EGFR under oxidative stress, we used confocal analysis to show that the receptor not only remains colocalized with caveolin-1 at the plasma membrane, but at longer time points, is also sorted to a perinuclear compartment via a clathrin-independent, caveolae-mediated pathway. Our findings indicate that although the EGFR associates with caveolin-1 constitutively, caveolin-1 is hyperphosphorylated only under oxidative stress, which is essential in transporting the EGFR to a perinuclear location, where it is not degraded and remains active. Thus, oxidative stress may have a role in tumorigenesis by not only activating the EGFR but also by promoting prolonged activation of the receptor both at the plasma membrane and within the cell. Activation of the epidermal growth factor (EGF)2 receptor (EGFR) by EGF results in the initiation of signal transduction cascades involved in cellular survival and proliferation. Therefore, to control cellular growth and tumorigenesis, the activation of the EGFR has to be tightly regulated in a process that includes degradation of the receptor. Binding of EGF to EGFR is rapidly followed by internalization of the membrane-bound receptor mainly through clathrin-coated pits and into early endosomes, which develop into late endosomes. There, the EGFR is either targeted to lysosomes for degradation or recycled to the plasma membrane (1-3). The inability of the EGFR to be down-regulated via clathrinmediated endocytosis and degradation has been linked to its oncogenicity (4, 5).H 2 O 2 -induced oxidative stress has been shown to activate and aberrantly phosphorylate the EGFR, which impedes the clathrin-mediated endocytosis and subsequent lysosomal degradation of the receptor (6 -8). This results in prolonged downstream activation of proliferative molecules such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) (9), and the lack of receptor turnover has been shown to mediate tumor promotion in non-neoplastic rat liver epithelial cells (10). To gain more insight into H 2 O 2 -induced EGFR signaling and hyperplastic responses, we examined the trafficking of the receptor under oxidative stress.Huang and Sorkin (11) have recently reported that knock-down of Grb2 by RNA interference inhibits clat...

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“…Similarly, gallic acid -a well-known strong antioxidant that is abundant in fruits, vegetables, green tea, and red wine -also has not been shown to prevent the inhibition of GJIC by hydrogen peroxide [56]. Since resveratrol does not decompose hydrogen peroxide (on the basis of direct measurements using ferrous ion oxidation and xylenol orange), the effects of resveratrol on GJIC are probably due to mechanisms other than antioxidant activity, such as the inhibition of MAPKs [13] and inactivation of the epidermal growth factor receptor [35].…”

Section: Resveratrolmentioning

confidence: 99%

The roles of polyphenols in cancer chemoprevention

2006

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Abstract.Oxidative stress imposed by reactive oxygen species (ROS) plays a crucial role in the pathophysiology associated with neoplasia, atherosclerosis, and neurodegenerative diseases. The ROS-induced development of cancer involves malignant transformation due to altered gene expression through epigenetic mechanisms as well as DNA mutations. Considerable attention has been focused on identifying naturally occurring antioxidative phenolic phytochemicals that are able to decrease ROS levels, but the efficacies of antioxidant therapies have been equivocal at best. Several studies have shown that some antioxidants exhibit prooxidant activity under certain conditions and potential carcinogenicity under others, and that dietary supplementation with large amounts of a single antioxidant may be deleterious to human health. This article reviews the intracellular signaling pathways that respond to oxidative stress and how they are modulated by naturally occurring polyphenols. The possible toxicity and carcinogenicity of polyphenols is also discussed.

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Hydrogen peroxide promotes transformation of rat liver non‐neoplastic epithelial cells through activation of epidermal growth factor receptor

Cited by 72 publications

References 39 publications

Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation

Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation

Epidermal Growth Factor Receptor Exposed to Oxidative Stress Undergoes Src- and Caveolin-1-dependent Perinuclear Trafficking

The roles of polyphenols in cancer chemoprevention

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