title: PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model.
abstract: Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione peroxidase (GPx) and iPLA2 activities. Even though several pathophysiological functions have been studied, the definitive role of PRDX6 in tumor growth is not clear. Here, we compared carcinogen-induced tumor growth in PRDX6-transgenic (Tg) mice and non-Tg mice to evaluate the roles of PRDX6 in lung tumor development. Urethane (1g/kg)-induced tumor incidence in PRDX6-Tg mice was significantly higher compared to non-Tg mice. In the tumors of PRDX6-Tg mice, the activation of JAK2/STAT3 and STAT3 DNA binding were also increased, accompanied by increased GPx and iPLA2 activities. PRDX6 was colocalized with JAK2 in tumor tissues and lung cancer cells and also showed physical interaction with JAK2. We found that increasing levels of PRDX6 increase the activation of the JAK2/STAT3 pathway. Furthermore, PRDX6-Tg mice showed altered cytokine levels in the tumors, especially leading to increased CCL5 levels. We validated that the activation of JAK2 was also decreased in lung tumors of CCR5(-/-) mice, and CCL5 increased the JAK2/STAT3 pathway in the lung cancer cells. Thus, our findings suggest that PRDX6 promotes lung tumor development via its mediated and CCL5-associated activation of the JAK2/STAT3 pathway.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Jo
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 150-716, Republic of Korea.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea. Electronic address: jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000818:Animals; D018946:Chemokine CCL5 / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054465:Peroxiredoxin VI / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014520:Urethane
chemical_list: C000592874:CCR5 protein, mouse; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D004273:DNA, Neoplasm; D019713:Receptors, CCR5; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014520:Urethane; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse; D005979:Glutathione Peroxidase; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse
keywords: Free radicals; GPx; JAK2; Lung cancer; PRDX6; STAT3; iPLA2