Overexpression of PRDX4 Modulates Tumor Microenvironment and Promotes Urethane-Induced Lung Tumorigenesis

Zheng, Jianbo; Guo, Xin; Nakamura, Yuka; Zhou, Xiaolei; Yamaguchi, Reimon; Zhang, Jing; Ishigaki, Yasuhito; Uramoto, Hidetaka; Yamada, Sohsuke

doi:10.1155/2020/8262730

Cited by 14 publications

(14 citation statements)

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“…A urethane (1 g/kg) i.p. injection of non-transgenic control and human Prx4-expressing transgenic mice for 16 weeks resulted in significantly more and bigger tumors in the transgenic group [ 117 ]. This increase in tumor burden was attributed to the suppressed apoptosis and enhanced proliferation in the tumors in the transgenic group.…”

Section: Prx4 and Cancermentioning

confidence: 99%

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer

et al. 2022

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Peroxiredoxin IV (Prx4) is a 2-Cysteine peroxidase with ubiquitous expression in human tissues. Prx4 scavenges hydrogen peroxide and participates in oxidative protein folding in the endoplasmic reticulum. In addition, Prx4 is secreted outside the cell. Prx4 is upregulated in several cancers and is a potential therapeutic target. We have summarized historical and recent advances in the structure, function and biological roles of Prx4, focusing on inflammatory diseases and cancer. Oxidative stress is known to activate pro-inflammatory pathways. Chronic inflammation is a risk factor for cancer development. Hence, redox enzymes such as Prx4 are important players in the crosstalk between inflammation and cancer. Understanding molecular mechanisms of regulation of Prx4 expression and associated signaling pathways in normal physiological and disease conditions should reveal new therapeutic strategies. Thus, although Prx4 is a promising therapeutic target for inflammatory diseases and cancer, further research needs to be conducted to bridge the gap to clinical application.

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Section: Prx4 and Cancermentioning

confidence: 99%

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer

et al. 2022

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“…A graphical representation of the effects of the overexpression of antioxidant genes on the induction, prevention, promotion, or suppression of tumor processes (based on an analysis of 130 studies) [ 58 , 63 , 66 , 87 , 88 , 89 , 90 , 103 , 104 , 105 , 114 , 117 , 159 , 173 , 174 , 175 , 192 , 201 , 210 , 230 , 232 , 233 , 234 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , …”

Section: Effects Of the Antioxidant Defense Genes Overexpression On C...mentioning

confidence: 99%

“…Increased resistance: γ-ray [66], urethane [159], photon radiation [160], 6-hydroxydopamine [153] Unchanged resistance: doxorubicin [154] PRDX5 in vitro…”

Section: Gstp1 In Vitromentioning

confidence: 99%

“…A graphical representation of the effects of the overexpression of antioxidant genes on the induction, prevention, promotion, or suppression of tumor processes (based on an analysis of 130 studies) [58,63,66,[87][88][89][90][103][104][105]114,117,159,[173][174][175]192,201,210,230,[232][233][234] is given in Figure 1. More detailed information and references to actual studies are provided in Table S2.…”

Section: Effects Of the Antioxidant Defense Genes Overexpression On C...mentioning

confidence: 99%

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Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review

et al. 2022

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Reactive oxygen species (ROS) are normal products of a number of biochemical reactions and are important signaling molecules. However, at the same time, they are toxic to cells and have to be strictly regulated by their antioxidant systems. The etiology and pathogenesis of many diseases are associated with increased ROS levels, and many external stress factors directly or indirectly cause oxidative stress in cells. Within this context, the overexpression of genes encoding the proteins in antioxidant systems seems to have become a viable approach to decrease the oxidative stress caused by pathological conditions and to increase cellular stress resistance. However, such manipulations unavoidably lead to side effects, the most dangerous of which is an increased probability of healthy tissue malignization or increased tumor aggression. The aims of the present review were to collect and systematize the results of studies devoted to the effects resulting from the overexpression of antioxidant system genes on stress resistance and carcinogenesis in vitro and in vivo. In most cases, the overexpression of these genes was shown to increase cell and organism resistances to factors that induce oxidative and genotoxic stress but to also have different effects on cancer initiation and promotion. The last fact greatly limits perspectives of such manipulations in practice. The overexpression of GPX3 and SOD3 encoding secreted proteins seems to be the “safest” among the genes that can increase cell resistance to oxidative stress. High efficiency and safety potential can also be found for SOD2 overexpression in combinations with GPX1 or CAT and for similar combinations that lead to no significant changes in H2O2 levels. Accumulation, systematization, and the integral analysis of data on antioxidant gene overexpression effects can help to develop approaches for practical uses in biomedical and agricultural areas. Additionally, a number of factors such as genetic and functional context, cell and tissue type, differences in the function of transcripts of one and the same gene, regulatory interactions, and additional functions should be taken into account.

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“…Previous studies indicate that Prx4 is upregulated in different types of human cancer, including glioma (12,13), lung cancer (14), leukemia (15), prostate cancer (16), colorectal cancer (17), and multiple myeloma (18). In the context of carcinogenesis, Prx4 promoted urethane-induced lung cancer through the increased phosphorylation of NF-κB p65 and c-Jun in transgenic mouse model study (19). In prostate cancer, the most common metastatic site is the bone, which is often the only clinically detectable site of metastasis (20), and depletion of Prx4 in prostate cancer cells can reduce the number of osteolytic lesions by inhibiting the differentiation of osteoclast (21).…”

mentioning

confidence: 96%