PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model

Yun, Hyung-Mun; Park, Kyung-Ran; Park, Mi Hee; Kim, Dae Hwan; Jo, Mi Ran; Kim, Ji Young; Kim, Eun-Cheol; Yoon, Do Young; Han, Sang Bae; Hong, Jin Tae

doi:10.1016/j.freeradbiomed.2014.12.022

Cited by 51 publications

(46 citation statements)

References 59 publications

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“…In this study, we found that JAK2/STAT3 pathway was a novel possible downstream of XCL1/XCR1, for that XCL1/XCR1 could significantly up-regulate the expression of p-JAK2 and p-STAT3 and the mRNA level of the targets of JAK2/STAT3, including PIM1, JunB and TTP. JAK2/STAT3 pathway was known to be markedly activated in NSCLC and promote cancer cell proliferation, invasion and metastasis [19,20]. Meanwhile, the overexpression of p-STAT3 was showed to be a strong predictor of poor prognosis among patients with NSCLC [21].…”

Section: Discussionmentioning

confidence: 99%

XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

Wang

Han

et al. 2015

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 99%

XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

Wang

Han

et al. 2015

Biochemical and Biophysical Research Communications

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“…An increase in the number and size of urethane-induced adenocarcinomas and the growth of A549 and NCI-H460 human lung cancer cells in mice was attributed to activation of the JAK2/STAT3 pathway, but the deletion of either the GPx activity (C47S-Prdx6) or the aiPLA2 activity (S32A-Prdx6) of Prdx6 had no effect on phosphorylated (activated) JAK2/STAT3 expression in these cells (127,140). Although the authors concluded that either enzymatic activity by itself could support activation of the pathway, this conclusion is suspect since either Based on these various studies, a preliminary conclusion is that aiPLA 2 activity can support tumor growth, invasiveness, and metastasis.…”

Section: Cancer and Carcinogenesismentioning

confidence: 99%

The phospholipase A2 activity of peroxiredoxin 6 [S]

Fisher

2018

Journal of Lipid Research

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Peroxiredoxin 6 (Prdx6) is a Ca 2+ -independent intracellular phospholipase A 2 (called aiPLA 2 )that is localized to cytosol, lysosomes, and lysosomal-related organelles. Activity is minimal at cytosolic pH but is increased significantly with enzyme phosphorylation, at acidic pH, and in the presence of oxidized phospholipid substrate; maximal activity with phosphorylated aiPLA 2 is ~2 µmol/min/mg protein. Prdx6 is a "moonlighting" protein that also expresses glutathione peroxidase and lysophosphatidylcholine acyl transferase activities.The catalytic site for aiPLA 2 activity is an S32-H26-D140 triad; S32-H26 is also the phospholipid binding site. Activity is inhibited by a serine "protease" inhibitor (diethyl p-nitrophenyl phosphate),an analogue of the PLA 2 transition state (1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol, MJ33), and by two naturally occurring proteins (surfactant protein A and p67 phox ), but not by bromoenol lactone. aiPLA 2 activity has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase (NOX2). The enzyme has been implicated in acute lung injury, carcinogenesis, neurodegenerative diseases, diabetes, male infertility, and sundry other conditions although its specific roles have not been well defined. Protein mutations and animal models are now available to further investigate the roles of Prdx6-aiPLA 2 activity in normal and pathological physiology.

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“…Xu et al [69] found that PRDX6 was highly expressed in the peri-tumoral tissues and played a critical role in inhibiting the carcinogenesis of hepatocellular carcinoma. However, Yun et al [70,71] demonstrated that PRDX6 promoted the development of lung cancer via JAK2/STAT3 pathway, its GPx and iPLA2 activities. The study of Raatikainen et al [52] showed that high PRDX6 expression was related to shortened biochemical recurrence-free survival and OS in prostate cancer patients after radical prostatectomy.…”

Section: Discussionmentioning

confidence: 99%

The prognostic values of the peroxiredoxins family in ovarian cancer

Zhu

2018

Bioscience Reports

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Purpose: Peroxiredoxins (PRDXs) are a family of antioxidant enzymes with six identified mammalian isoforms (PRDX1–6). PRDX expression is up-regulated in various types of solid tumors; however, individual PRDX expression, and its impact on prognostic value in ovarian cancer patients, remains unclear.Methods: PRDXs family protein expression profiles in normal ovarian tissues and ovarian cancer tissues were examined using the Human Protein Atlas database. Then, the prognostic roles of PRDX family members in several sets of clinical data (histology, pathological grades, clinical stages, and applied chemotherapy) in ovarian cancer patients were investigated using the Kaplan–Meier plotter.Results: PRDXs family protein expression in ovarian cancer tissues was elevated compared with normal ovarian tissues. Meanwhile, elevated expression of PRDX3, PRDX5, and PRDX6 mRNAs showed poorer overall survival (OS); PRDX5 and PRDX6 also predicted poor progression-free survival (PFS) for ovarian cancer patients. Furthermore, PRDX3 played significant prognostic roles, particularly in poor differentiation and late-stage serous ovarian cancer patients. Additionally, PRDX5 predicted a lower PFS in all ovarian cancer patients treated with Platin, Taxol, and Taxol+Platin chemotherapy. PRDX3 and PRDX6 also showed poor PFS in patients treated with Platin chemotherapy. Furthermore, PRDX3 and PRDX5 indicated lower OS in patients treated with these three chemotherapeutic agents. PRDX6 predicted a poorer OS in patients treated with Taxol and Taxol+Platin chemotherapy.Conclusion: These results suggest that there are distinct prognostic values of PRDX family members in patients with ovarian cancer, and that the expression of PRDX3, PRDX5, and PRDX6 mRNAs are a useful prognostic indicator in the effect of chemotherapy in ovarian cancer patients.

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PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model

Cited by 51 publications

References 59 publications

XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

The phospholipase A2 activity of peroxiredoxin 6 [S]

The prognostic values of the peroxiredoxins family in ovarian cancer

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