БИОХИМИЯ, 2019, том 84, вып. 2, с. 147–171
УДК 577.321
Каталитическая и сигнально-регуляторная роль пероксиредоксинов в канцерогенезе
Обзор
Институт биофизики клетки РАН, Пущино Московской обл., Россия; электронная почта: sharapov.mars@gmail.com
Поступила в редакцию 29.03.2018
После доработки 26.08.2018
Принята к публикации 26.08.2018
DOI: 10.1134/S0320972519020015
КЛЮЧЕВЫЕ СЛОВА: пероксиредоксины, клеточная сигнализация, окислительный стресс, канцерогeнез.
Аннотация
Раковые клетки испытывают мощный окислительный стресс из-за накопления внутренних нарушений метаболизма и действия внешних факторов. Для выживания раковые клетки обладают высокоэффективной системой антиоксидантной защиты, одним из важнейших элементов которой являются пероксиредоксины (Рrx). Рrx — эволюционно древнее семейство селен-независимых пероксидаз, которые восстанавливают широкий спектр органических и неорганических гидропероксидов в клетке и межклеточном пространстве. Для некоторых Рrx показана шаперонная и фосфолипазная активность. Рrx играют важную роль в поддержании окислительно-восстановительного гомеостаза клеток, препятствуют окислению и агрегации важных регуляторных белков, тем самым, они оказывают влияние на многие сигнально-регуляторные пути клетки. Рrx участвуют в регуляции роста, дифференцировки и апоптоза клеток. Благодаря своей многофункциональности и широкой представленности во всех тканях и органах, Рrx участвуют в развитии или подавлении многих патологических состояний, среди которых особое место занимают онкологические заболевания. В обзоре обсуждается роль Рrx в канцерогенезе и развитии различных форм рака. Понимание молекулярных механизмов этих процессов способствут развитию новых направлений в предупреждении и лечении онкологических заболеваний.
Текст статьи
Сноски
* Адресат для корреспонденции.
Финансирование
Работа поддержана грантом Президента РФ (MK-2261.2017.4), грантом РФФИ (17-04-00356-а, 17-44-500476р_а) и программой Президиума РАН «Молекулярная и клеточная биология и постгеномные технологии».
Конфликт интересов
Авторы заявляют об отсутствии конфликта интересов.
Список литературы
1. Sharapov, M.G., Ravin, V.K., and Novoselov, V.I. (2014) Peroxiredoxins as multifunctional enzymes, Mol. Biol. (Moscow), 48, 520–545.
2. Rhee, S.G., and Kil, I.S. (2016) Multiple functions and regulation of mammalian peroxiredoxins, Annu. Rev. Biochem., 85, 1–27.
3. Perkins, A., Poole, L.B., and Karplus, P.A. (2014) Tuning of peroxiredoxin catalysis for various physiological roles, Biochemistry, 53, 7693–7705.
4. Jarvis, R.M., Hughes, S.M., and Ledgerwood, E.C. (2012) Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells, Free Radic. Biol. Med., 53, 1522–1530.
5. Neumann, C.A., Krause, D.S., Carman, C. V, Das, S., Dubey, D.P., Abraham, J.L., Bronson, R.T., Fujiwara, Y., Orkin, S.H., and Van Etten, R.A. (2003) Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression, Nature, 424, 561–565.
6. Riddell, J.R., Maier, P., Sass, S.N., Moser, M.T., Foster, B.A., and Gollnick, S.O. (2012) Peroxiredoxin 1 stimulates endothelial cell expression of VEGF via TLR4 dependent activation of HIF-1α, PLoS One, 7, e50394.
7. Cao, J., Schulte, J., Knight, A., Leslie, N.R., Zagozdzon, A., Bronson, R., Manevich, Y., Beeson, C., and Neumann, C.A. (2009) Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity, EMBO J., 28, 1505–1517.
8. Nassour, H., Wang, Z., Saad, A., Papaluca, A., Brosseau, N., Affar, E.B., Alaoui-Jamali, M.A., and Ramotar, D. (2016) Peroxiredoxin 1 interacts with and blocks the redox factor APE1 from activating interleukin-8 expression, Sci. Rep., 6, 29389.
9. Egler, R.A., Fernandes, E., Rothermund, K., Sereika, S., de Souza-Pinto, N., Jaruga, P., Dizdaroglu, M., and Prochownik, E. V. (2005) Regulation of reactive oxygen species, DNA damage, and c-Myc function by peroxiredoxin 1, Oncogene, 24, 8038–8050.
10. Morinaka, A., Funato, Y., Uesugi, K., and Miki, H. (2011) Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis, Oncogene, 30, 4208–4218.
11. Godfrey, R., Arora, D., Bauer, R., Stopp, S., Muller, J.P., Heinrich, T., Bohmer, S.-A., Dagnell, M., Schnetzke, U., Scholl, S., Ostman, A., and Bohmer, F.-D. (2012) Cell transformation by FLT3 ITD in acute myeloid leukemia involves oxidative inactivation of the tumor suppressor protein-tyrosine phosphatase DEP-1/ PTPRJ, Blood, 119, 4499–4511.
12. Park, Y.-H., Kim, S.-U., Lee, B.-K., Kim, H.-S., Song, I.-S., Shin, H.-J., Han, Y.-H., Chang, K.-T., Kim, J.-M., Lee, D.-S., Kim, Y.-H., Choi, C.-M., Kim, B.-Y., and Yu, D.-Y. (2013) Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway, Antioxid. Redox Signal., 19, 482–496.
13. Shiota, M., Yokomizo, A., Kashiwagi, E., Takeuchi, A., Fujimoto, N., Uchiumi, T., and Naito, S. (2011) Peroxiredoxin 2 in the nucleus and cytoplasm distinctly regulates androgen receptor activity in prostate cancer cells, Free Radic. Biol. Med., 51, 78–87.
14. Zhang, S., Fu, Z., Wei, J., Guo, J., Liu, M., and Du, K. (2015) Peroxiredoxin 2 is involved in vasculogenic mimicry formation by targeting VEGFR2 activation in colorectal cancer, Med. Oncol., 32, 1–8.
15. Lu, W., Fu, Z., Wang, H., Feng, J., Wei, J., and Guo, J. (2014) Peroxiredoxin 2 knockdown by RNA interference inhibits the growth of colorectal cancer cells by downregulating Wnt/β-catenin signaling, Cancer Lett., 343, 190–199.
16. Wang, R., Wei, J., Zhang, S., Wu, X., Guo, J., Liu, M., Du, K., Xu, J., Peng, L., Lv, Z., You, W., Xiong, Y., and Fu, Z. (2016) Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer, Oncotarget, 7, 86816–86828.
17. Luo, W., Chen, I., Chen, Y., Alkam, D., Wang, Y., and Semenza, G.L. (2016) PRDX2 and PRDX4 are negative regulators of hypoxia-inducible factors under conditions of prolonged hypoxia, Oncotarget, 7, 6379–6397.
18. Sobotta, M.C., Liou, W., Stocker, S., Talwar, D., Oehler, M., Ruppert, T., Scharf, A.N.D., and Dick, T.P. (2015) Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling, Nat. Chem. Biol., 11, 64–70.
19. Lee, K.W., Lee, D.J., Lee, J.Y., Kang, D.H., Kwon, J., and Kang, S.W. (2011) Peroxiredoxin II restrains DNA damage-induced death in cancer cells by positively regulating JNK-dependent DNA repair, J. Biol. Chem., 286, 8394–8404.
20. Song, I.-S., Kim, H.-K., Jeong, S.-H., Lee, S.-R., Kim, N., Rhee, B.D., Ko, K.S., and Han, J. (2011) Mitochondrial peroxiredoxin III is a potential target for cancer therapy, Int. J. Mol. Sci., 12, 7163–7185.
21. Xi, H., Gao, Y.-H., Han, D.-Y., Li, Q.-Y., Feng, L.-J., Zhang, W., Ji, G., Xiao, J.-C., Zhang, H.-Z., and Wei, Q. (2014) Hypoxia inducible factor-1α suppresses Peroxiredoxin 3 expression to promote proliferation of CCRCC cells, FEBS Lett., 588, 3390–3394.
22. Kim, Y.S., Lee, H.L., Lee, K.B., Park, J.H., Chung, W.Y., Lee, K.S., Sheen, S.S., Park, K.J., and Hwang, S.C. (2011) Nuclear factor E2-related factor 2 dependent overexpression of sulfiredoxin and peroxiredoxin III in human lung cancer, Korean J. Intern. Med., 26, 304–313.
23. Jeong, H.J., Jeong, H.W., Song, S.S., Kang, J.W., Seo, J.H., Lee, Y.H., Lee, K.S., and Kim, D.W. (2011) Upregulation of peroxiredeoxin III in the hippocampus of acute immobilization stress model rats and the Foxo3a-dependent expression in PC12 cells, Cell. Mol. Neurobiol., 31, 1041–1046.
24. Tavender, T.J., Springate, J.J., and Bulleid, N.J. (2010) Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum, EMBO J., 29, 4185–4197.
25. Zhang, Y., Emmanuel, N., Kamboj, G., Chen, J., Shurafa, M., van Dyke, D.L., Wiktor, A., and Rowley, J.D. (2004) PRDX4, a member of the peroxiredoxin family, is fused to AML1 (RUNX1) in an acute myeloid leukemia patient with a t(X;21)(p22;q22), Genes Chromosom. Cancer, 40, 365–370.
26. Wei, Q., Jiang, H., Xiao, Z., Baker, A., Young, M.R., Veenstra, T.D., and Colburn, N.H. (2011) Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling, Proc. Natl. Acad. Sci. USA, 108, 7004–7009.
27. Walbrecq, G., Wang, B., Becker, S., Hannotiau, A., Fransen, M., and Knoops, B. (2015) Antioxidant cytoprotection by peroxisomal peroxiredoxin-5, Free Radic. Biol. Med., 84, 215–226.
28. Ahn, H.-M., Yoo, J.-W., Lee, S., Lee, H.J., Lee, H.-S., and Lee, D.-S. (2017) Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer, Biochem. Biophys. Res. Commun., 487, 580–586.
29. Banmeyer, I., Marchand, C., Clippe, A., and Knoops, B. (2005) Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide, FEBS Lett., 579, 2327–2333.
30. Wu, Y., Feinstein, S.I., Manevich, Y., Chowdhury, I., Pak, J.H., Kazi, A., Dodia, C., Speicher, D.W., and Fisher, A.B. (2009) Mitogen-activated protein kinase-mediated phosphorylation of peroxiredoxin 6 regulates its phospholipase A(2) activity, Biochem. J., 419, 669–679.
31. Zha, X., Wu, G., Zhao, X., Zhou, L., Zhang, H., Li, J., Ma, L., and Zhang, Y. (2015) PRDX6 protects ARPE-19 cells from oxidative damage via PI3K/AKT signaling, Cell. Physiol. Biochem., 36, 2217–2228.
32. Choi, H., Chang, J.-W., and Jung, Y.-K. (2011) Peroxiredoxin 6 interferes with TRAIL-induced death-inducing signaling complex formation by binding to death effector domain caspase, Cell Death Differ., 18, 405–414.
33. Yun, H.-M., Park, K.-R., Park, M.H., Kim, D.H., Jo, M.R., Kim, J.Y., Kim, E.-C., Yoon, D.Y., Han, S.B., and Hong, J.T. (2015) PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model, Free Radic. Biol. Med., 80, 136–144.
34. Peskin, A. V, Dickerhof, N., Poynton, R.A., Paton, L.N., Pace, P.E., Hampton, M.B., and Winterbourn, C.C. (2013) Hyperoxidation of peroxiredoxins 2 and 3: rate constants for the reactions of the sulfenic acid of the peroxidatic cysteine, J. Biol. Chem., 288, 14170–14177.
35. Jung, C.L., Choi, H.I., Yu, S.P., Hyung, W.N., Hyun, A.W., Kwon, K.S., Yu, S.K., Sue, G.R., Kim, K., and Chae, H.Z. (2008) Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity, J. Biol. Chem., 283, 28873–28880.
36. Kim, S.Y., Jo, H.-Y., Kim, M.H., Cha, Y.Y., Choi, S.W., Shim, J.-H., Kim, T.J., Lee, K.-Y. (2008) H2O2-dependent hyperoxidation of peroxiredoxin 6 (Prdx6) plays a role in cellular toxicity via up-regulation of iPLA2 activity, J. Biol. Chem., 283, 33563–33568.
37. Venereau, E., Ceriotti, C., and Bianchi, M.E. (2015) DAMPs from cell death to new life, Front. Immunol., 6, 422.
38. Park, M.H., Jo, M., Kim, Y.R., Lee, C.-K., and Hong, J.T. (2016) Roles of peroxiredoxins in cancer, neurodegenerative diseases and inflammatory diseases, Pharmacol. Ther., 163, 1–23.
39. Poschmann, G., Grzendowski, M., Stefanski, A., Bruns, E., Meyer, H.E., and Stuhler, K. (2015) Redox proteomics reveal stress responsive proteins linking peroxiredoxin-1 status in glioma to chemosensitivity and oxidative stress, Biochim. Biophys. Acta, 1854, 624–631.
40. Zhang, J., Jing, X., Niu, W., Zhang, M., Ge, L., Miao, C., and Tang, X. (2016) Peroxiredoxin 1 has an anti-apoptotic role via apoptosis signal-regulating kinase 1 and p38 activation in mouse models with oral precancerous lesions, Oncol. Lett., 12, 413–420.
41. Kim, Y.-J., Lee, W.-S., Ip, C., Chae, H.-Z., Park, E.-M., Park, Y.-M. (2006) Prx1 suppresses radiation-induced c-Jun NH2-terminal kinase signaling in lung cancer cells through interaction with the glutathione S-transferase Pi/c-Jun NH2-terminal kinase complex, Cancer Res., 66, 7136–7142.
42. Jiang, H., Wu, L., Mishra, M., Chawsheen, H.A., and Wei, Q. (2014) Expression of peroxiredoxin 1 and 4 promotes human lung cancer malignancy, Am. J. Cancer Res., 4, 445–460.
43. Gong, F., Hou, G., Liu, H., and Zhang, M. (2015) Peroxiredoxin 1 promotes tumorigenesis through regulating the activity of mTOR/p70S6K pathway in esophageal squamous cell carcinoma, Med. Oncol., 32, 455.
44. Morinaka, A., Funato, Y., Uesugi, K., and Miki, H. (2011) Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis, Oncogene, 30, 4208–4218.
45. Wang, X., He, S., Sun, J.-M., Delcuve, G.P., and Davie, J.R. (2010) Selective association of peroxiredoxin 1 with genomic DNA and COX-2 upstream promoter elements in estrogen receptor negative breast cancer cells, Mol. Biol. Cell, 21, 2987–2995.
46. Du, Z.-X., Yan, Y., Zhang, H.-Y., Liu, B.-Q., Gao, Y.-Y., Niu, X.-F., Guan, Y., Meng, X., and Wang, H.-Q. (2010) Suppression of MG132-mediated cell death by peroxiredoxin 1 through influence on ASK1 activation in human thyroid cancer cells, Endocr. Relat. Cancer, 17, 553–560.
47. Nicolussi, A., D’Inzeo, S., Mincione, G., Buffone, A., Di Marcantonio, M.C., Cotellese, R., Cichella, A., Capalbo, C., Di Gioia, C., Nardi, F., Giannini, G., and Coppa, A. (2014) PRDX1 and PRDX6 are repressed in papillary thyroid carcinomas via BRAF V600E-dependent and -independent mechanisms, Int. J. Oncol., 44, 548–556.
48. Taniuchi, K., Furihata, M., Hanazaki, K., Iwasaki, S., Tanaka, K., Shimizu, T., Saito, M., and Saibara, T. (2015) Peroxiredoxin 1 promotes pancreatic cancer cell invasion by modulating p38 MAPK activity, Pancreas, 44, 331–340.
49. Sun, Q.-K., Zhu, J.-Y., Wang, W., Lv, Y., Zhou, H.-C., Yu, J.-H., Xu, G.-L., Ma, J.-L., Zhong, W., and Jia, W.-D. (2014) Diagnostic and prognostic significance of peroxiredoxin 1 expression in human hepatocellular carcinoma, Med. Oncol., 31, 786.
50. Quan, C., Cha, E.-J., Lee, H.-L., Han, K.H., Lee, K.M., and Kim, W.-J. (2006) Enhanced expression of peroxiredoxin I and VI correlates with development, recurrence and progression of human bladder cancer, J. Urol., 175, 1512–1516.
51. Kim, K., Yu, M., Han, S., Oh, I., Choi, Y.-J., Kim, S., Yoon, K., Jung, M., and Choe, W. (2009) Expression of human peroxiredoxin isoforms in response to cervical carcinogenesis, Oncol. Rep., 21, 1391–1396.
52. Chhipa, R.R., Lee, K.-S., Onate, S., Wu, Y., and Ip, C. (2009) Prx1 ehances androgen receptor function in prostate cancer cells by increasing receptor affinity to dihydrotestosterone, Mol. Cancer Res., 7, 1543–1552.
53. Chu, G., Li, J., Zhao, Y., Liu, N., Zhu, X., Liu, Q., Wei, D., and Gao, C. (2016) Identification and verification of PRDX1 as an inflammation marker for colorectal cancer progression, Am. J. Transl. Res., 8, 842–859.
54. Trzeciecka, A., Klossowski, S., Bajor, M., Zagozdzon, R., Gaj, P., Muchowicz, A., Malinowska, A., Czerwoniec, A., Barankiewicz, J., Domagala, A., Chlebowska, J., Prochorec-Sobieszek, M., Winiarska, M., Ostaszewski, R., Gwizdalska, I., Golab, J., Nowis, D., and Firczuk, M. (2016) Dimeric peroxiredoxins are druggable targets in human Burkitt lymphoma, Oncotarget, 7, 1717–1731.
55. Hintsala, H.-R., Soini, Y., Haapasaari, K.-M., and Karihtala, P. (2015) Dysregulation of redox-state-regulating enzymes in melanocytic skin tumours and the surrounding microenvironment, Histopathology, 67, 348–357.
56. Park, J.H., Kim, Y.S., Lee, H.L., Shim, J.Y., Lee, K.S., Oh, Y.J., Shin, S.S., Choi, Y.H., Park, K.J., Park, R.W., and Hwang, S.C. (2006) Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung, Respirology, 11, 269–275.
57. Wang, T., Diaz, A.J.G., and Yen, Y. (2014) The role of peroxiredoxin II in chemoresistance of breast cancer cells, Breast Cancer Targets Ther., 6, 73–80.
58. Park, Y.-H., Kim, S.-U., Kwon, T.-H., Kim, J.-M., Song, I.-S., Shin, H.-J., Lee, B.-K., Bang, D.-H., Lee, S.-J., Lee, D.-S., Chang, K.-T., Kim, B.-Y., and Yu, D.-Y. (2016) Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway, Oncogene, 35, 3503–3513.
59. Memon, A.A., Chang, J.W., Oh, B.R., and Yoo, Y.J. (2005) Identification of differentially expressed proteins during human urinary bladder cancer progression, Cancer Detect. Prev., 29, 249–255.
60. Lee, D.J., Kang, D.H., Choi, M., Choi, Y.J., Lee, J.Y., Park, J.H., Park, Y.J., Lee, K.W., and Kang, S.W. (2013) Peroxiredoxin-2 represses melanoma metastasis by increasing E-cadherin/в-catenin complexes in adherens junctions, Cancer Res., 73, 4744–4757.
61. Nonn, L., Berggren, M., and Powis, G. (2003) Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis, Mol. Cancer Res., 1, 682–689.
62. Karihtala, P., Mantyniemi, A., Kang, S.W., Kinnula, V.L., and Soini, Y. (2003) Peroxiredoxins in breast carcinoma, Clin. Cancer Res., 9, 3418–3424.
63. Wang, Y.-G., Li, L., Liu, C.-H., Hong, S., and Zhang, M.-J. (2014) Peroxiredoxin 3 is resistant to oxidation-induced apoptosis of Hep-3b cells, Clin. Transl. Oncol., 16, 561–566.
64. Wang, X., Wang, H., and Li, X. (2013) Peroxiredoxin III protein expression is associated with platinum resistance in epithelial ovarian cancer, Tumour Biol., 34, 2275–2281.
65. Byun, J.M., Kim, S.S., Kim, K.T., Kang, M.S., Jeong, D.H., Lee, D.S., Jung, E.J., Kim, Y.N., Han, J., Song, I.S., Lee, K.B., and Sung, M.S. (2018) Overexpression of peroxiredoxin-3 and -5 is a potential biomarker for prognosis in endometrial cancer, Oncol. Lett., 15, 5111–5118.
66. Hu, J.-X., Gao, Q., and Li, L. (2013) Peroxiredoxin 3 is a novel marker for cell proliferation in cervical cancer, Biomed. Rep., 1, 228–230.
67. Whitaker, H.C., Patel, D., Howat, W.J., Warren, A.Y., Kay, J.D., Sangan, T., Marioni, J.C., Mitchell, J., Aldridge, S., Luxton, H.J., Massie, C., Lynch, A.G., and Neal, D.E. (2013) Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress, Br. J. Cancer, 109, 983–993.
68. Wu, X.Y., Fu, Z.X., and Wang, X.H. (2010) Peroxiredoxins in colorectal neoplasms, Histol. Histopathol., 25, 1297–1303.
69. Kim, T.H., Song, J., Alcantara Llaguno, S.R., Murnan, E., Liyanarachchi, S., Palanichamy, K., Yi, J.-Y., Viapiano, M.S., Nakano, I., Yoon, S.O., Wu, H., Parada, L.F., and Kwon, C.-H. (2012) Suppression of peroxiredoxin 4 in glioblastoma cells increases apoptosis and reduces tumor growth, PLoS One, 7, e42818.
70. Chang, K.-P., Yu, J.-S., Chien, K.-Y., Lee, C.-W., Liang, Y., Liao, C.-T., Yen, T.-C., Lee, L.-Y., Huang, L.-L., Liu, S.-C., Chang, Y.-S., and Chi, L.-M. (2011) Identification of PRDX4 and P4HA2 as metastasis-associated proteins in oral cavity squamous cell carcinoma by comparative tissue proteomics of microdissected specimens using iTRAQ technology, J. Proteome Res., 10, 4935–4947.
71. Chung, J.C., Oh, M.J., Choi, S.H., and Bae, C.D. (2008) Proteomic analysis to identify biomarker proteins in pancreatic ductal adenocarcinoma, ANZ J. Surg., 78, 245–251.
72. Lin, J.-F., Xu, J., Tian, H.-Y., Gao, X., Chen, Q.-X., Gu, Q., Xu, G.-J., Song, J., and Zhao, F.-K. (2007) Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis, Int. J. Cancer, 121, 2596–2605.
73. Yi, N., Xiao, M.B., Ni, W.K., Jiang, F., Lu, C.H., and Ni, R.-Z. (2014) High expression of peroxiredoxin 4 affects the survival time of colorectal cancer patients, but is not an independent unfavorable prognostic factor, Mol. Clin. Oncol., 2, 767–772.
74. Palande, K.K., Beekman, R., van der Meeren, L.E., Beverloo, H.B., Valk, P.J., Touw, I.P. (2011) The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia, PLoS One, 6, 6–11.
75. De Simoni, S., Goemaere, J., and Knoops, B. (2008) Silencing of peroxiredoxin 3 and peroxiredoxin 5 reveals the role of mitochondrial peroxiredoxins in the protection of human neuroblastoma SH-SY5Y cells toward MPP+, Neurosci. Lett., 433, 219–224.
76. Lehtonen, S.T., Svensk, A.-M., Soini, Y., Paakko, P., Hirvikoski, P., Kang, S.W., Saily, M., and Kinnula, V.L. (2004) Peroxiredoxins, a novel protein family in lung cancer, Int. J. Cancer, 111, 514–521.
77. Seo, M.J., Liu, X., Chang, M., and Park, J.H. (2012) GATA-binding protein 1 is a novel transcription regulator of peroxiredoxin 5 in human breast cancer cells, Int. J. Oncol., 40, 655–664.
78. Liu, F., Zhang, Y., Men, T., Jiang, X., Yang, C., Li, H., Wei, X., Yan, D., Feng, G., Yang, J., Bergquist, J., Wang, B., Jiang, W., Mi, J., and Tian, G. (2017) Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor B signaling pathway, Oncotarget, 8, 22059–22075.
79. Fernandez-Ranvier, G.G., Weng, J., Yeh, R.-F., Shibru, D., Khafnashar, E., Chung, K.-W., Hwang, J., Duh, Q.Y., Clark, O.H., and Kebebew, E. (2008) Candidate diagnostic markers and tumor suppressor genes for adrenocortical carcinoma by expression profile of genes on chromosome 11q13, World J. Surg., 32, 873–881.
80. Shiota, M., Izumi, H., Miyamoto, N., Onitsuka, T., Kashiwagi, E., Kidani, A., Hirano, G., Takahashi, M., Ono, M., Kuwano, M., Naito, S., Sasaguri, Y., and Kohno, K. (2008) Ets regulates peroxiredoxin1 and 5 expressions through their interaction with the high-mobility group protein B1, Cancer Sci., 99, 1950–1959.
81. Su, D.M., Zhang, Q., Wang, X., He, P., Zhu, Y.J., Zhao, J., Rennert, O.M., and Su, Y.A. (2009) Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy, Mol. Cancer Ther., 8, 1292–1304.
82. Park, C.-K., Kim, J.H., Moon, M.J., Jung, J.H., Lim, S.-Y., Park, S.-H., Kim, J.-H., Kim, D.G., Jung, H.-W., Cho, B.-K., and Paek, S.H. (2008) Investigation of molecular factors associated with malignant transformation of oligodendroglioma by proteomic study of a single case of rapid tumor progression, J. Cancer Res. Clin. Oncol., 134, 255–262.
83. Yun, H.-M., Park, K.-R., Lee, H.P., Lee, D.H., Jo, M., Shin, D.H., Yoon, D.-Y., Han, S.B., and Hong, J.T. (2014) PRDX6 promotes lung tumor progression via its GPx and iPLA2 activities, Free Radic. Biol. Med., 69, 367–376.
84. Chang, X.-Z., Li, D.-Q., Hou, Y.-F., Wu, J., Lu, J.-S., Di, G.-H., Jin, W., Ou, Z.-L., Shen, Z.-Z., and Shao, Z.-M. (2007) Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer, Breast Cancer Res., 9, 1–15.
85. Fujita, Y., Nakanishi, T., Hiramatsu, M., Mabuchi, H., Miyamoto, Y., Miyamoto, A., Shimizu, A., and Tanigawa, N. (2006) Proteomics-based approach identifying autoantibody against peroxiredoxin VI as a novel serum marker in esophageal squamous cell carcinoma, Clin. Cancer Res., 12, 6415–6420.
86. Hoshino, I., Nagata, M., Takiguchi, N., Nabeya, Y., Ikeda, A., Yokoi, S., Kuwajima, A., Tagawa, M., Matsushita, K., Satoshi, Y., and Hideaki, S. (2017) Panel of autoantibodies against multiple tumor-associated antigens for detecting gastric cancer, Cancer Sci., 108, 308–315.
87. Walsh, B., Pearl, A., Suchy, S., Tartaglio, J., Visco, K., and Phelan, S.A. (2009) Overexpression of Prdx6 and resistance to peroxide-induced death in Hepa1-6 cells: Prdx suppression increases apoptosis, Redox Rep., 14, 275–284.
88. Pak, J.H., Choi, W.H., Lee, H.M., Joo, W.-D., Kim, J.-H., Kim, Y.-T., Kim, Y.-M., and Nam, J.-H. (2011) Peroxiredoxin 6 overexpression attenuates cisplatin-induced apoptosis in human ovarian cancer cells, Cancer Invest., 29, 21–28.
89. Raatikainen, S., Aaaltomaa, S., Karja, V., and Soini, Y. (2015) Increased peroxiredoxin 6 expression predicts biochemical recurrence in prostate cancer patients after radical prostatectomy, Anticancer Res., 6470, 6465–6470.
90. Schmitt, A., Schmitz, W., Hufnagel, A., Schartl, M., and Meierjohann, S. (2015) Peroxiredoxin 6 triggers melanoma cell growth by increasing arachidonic acid-dependent lipid signalling, Biochem. J., 471, 267–279.
91. Zhang, M., Hou, M., Ge, L., Miao, C., Zhang, J., Jing, X., Shi, N., Chen, T., and Tang, X. (2014) Induction of peroxiredoxin 1 by hypoxia regulates heme oxygenase-1 via NF-kB in oral cancer, PLoS One, 9, e105994.
92. Chang, J.W., Lee, S.H., Lu, Y., and Yoo, Y.J. (2006) Transforming growth factor-beta1 induces the non-classical secretion of peroxiredoxin-I in A549 cells, Biochem. Biophys. Res. Commun., 345, 118–123.
93. Riddell, J.R., Bshara, W., Moser, M.T., Spernyak, J.A., Foster, B.A., and Gollnick, S.O. (2011) Peroxiredoxin 1 controls prostate cancer growth through Toll-like receptor 4-dependent regulation of tumor vasculature, Cancer Res., 71, 1637–1646.
94. Aeby, E., Ahmed, W., Redon, S., Simanis, V., and Lingner, J. (2016) Peroxiredoxin 1 protects telomeres from oxidative damage and preserves telomeric DNA for extension by telomerase, Cell Rep., 17, 3107–3114.
95. Lee, W., Choi, K.-S., Riddell, J., Ip, C., Ghosh, D., Park, J.-H., and Park, Y.-M. (2007) Human peroxiredoxin 1 and 2 are not duplicate proteins: the unique presence of Cys83 in Prx1 underscores the structural and functional differences between Prx1 and Prx2, J. Biol. Chem., 282, 22011–22022.
96. Diaz, A.J.G., Tamae, D., Yen, Y., Li, J., and Wang, T. (2013) Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II, Breast Cancer Targets Ther., 5, 87–101.
97. Zhang, Y.-G., Wang, L., Kaifu, T., Li, J., Li, X., and Li, L. (2016) Featured article: accelerated decline of physical strength in peroxiredoxin-3 knockout mice, Exp. Biol. Med., 241, 1395–1400.
98. Cunniff, B., Benson, K., Stumpff, J., Newick, K., Held, P., Taatjes, D., Joseph, J., Kalyanaraman, B., and Heintz, N.H. (2013) Mitochondrial-targeted nitroxides disrupt mitochondrial architecture and inhibit expression of peroxiredoxin 3 and FOXM1 in malignant mesothelioma cells, J. Cell. Physiol., 228, 835–845.
99. Abdul Rahman Sazli, F., Jubri, Z., Abdul Rahman, M., Karsani, S.A., Md Top, A.G., Wan Ngah, W.Z. (2015) Gamma-tocotrienol treatment increased peroxiredoxin-4 expression in HepG2 liver cancer cell line, BMC Complement. Altern. Med., 15, 1–7.
100. Rafiei, S., Tiedemann, K., Tabaries, S., Siegel, P.M., and Komarova, S. V. (2015) Peroxiredoxin 4: a novel secreted mediator of cancer induced osteoclastogenesis, Cancer Lett., 361, 262–270.
101. Shah, F., Goossens, E., Atallah, N.M., Grimard, M., Kelley, M.R., and Fishel, M.L. (2017) APE1/Ref-1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single-cell RNA sequencing, Mol. Oncol., 11, 1711–1732.
102. Fisher, A.B., Vasquez-Medina, J.P., Dodia, C., Sorokina, E.M., Tao, J.-Q.Q., and Feinstein, S.I. (2018) Peroxiredoxin 6 phospholipid hydroperoxidase activity in the repair of peroxidized cell membranes, Redox Biol., 14, 41–46.
103. Liu, G.-Y., Shi, J.-X., Shi, S.-L., Liu, F., Rui, G., Li, X., Gao, L.-B., Deng, X.-L., and Li, Q.-F. (2017) Nucleophosmin regulates intracellular oxidative stress homeostasis via antioxidant PRDX6, J. Cell. Biochem., 118, 4697–4707.
104. Gallagher, B.M., and Phelan, S.A. (2007) Investigating transcriptional regulation of Prdx6 in mouse liver cells, Free Radic. Biol. Med., 42, 1270–1277.
105. Park, M.H., Yun, H.-M., Hwang, C.J., Park, S.I., Han, S.B., Hwang, D.Y., Yoon, D.-Y., Kim, S., and Hong, J.T. (2017) Presenilin mutation suppresses lung tumorigenesis via inhibition of peroxiredoxin 6 activity and expression, Theranostics, 7, 3624–3637.
106. Hwang, K.E., Park, C., Seol, C.H., Hwang, Y.R., Hwang, J.S., Jung, J.W., Choi, K.H., Jeong, E.T., and Kim, H.R. (2013) Elevated Prx1 provides resistance to docetaxel, but is not associated with predictive significance in lung cancer, Tuberc. Respir. Dis. (Seoul), 75, 59–66.
107. Yo, Y. Do, Chung, Y.M., Park, J.K., Ahn, C.M., Kim, S.K., and Kim, H.J. (2002) Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death, Exp. Mol. Med., 34, 273–277.
108. Soethoudt, M., Peskin, A. V, Dickerhof, N., Paton, L.N., Pace, P.E., and Winterbourn, C.C. (2014) Interaction of adenanthin with glutathione and thiol enzymes: selectivity for thioredoxin reductase and inhibition of peroxiredoxin recycling, Free Radic. Biol. Med., 77, 331–339.
109. Wang, F., Lin, F., Zhang, P., Ni, W., Bi, L., Wu, J., and Jiang, L. (2015) Thioredoxin-1 inhibitor, 1-methylpropyl 2-imidazolyl disulfide, inhibits the growth, migration and invasion of colorectal cancer cell lines, Oncol. Rep., 33, 967–73.
110. Kim, H., Lee, G.-R., Kim, J., Baek, J.Y., Jo, Y.-J., Hong, S.-E., Kim, S.H., Lee, J., Lee, H.I., Park, S.-K., Kim, H.M., Lee, H.J., Chang, T.-S., Rhee, S.G., Lee, J.-S., and Jeong, W. (2016) Sulfiredoxin inhibitor induces preferential death of cancer cells through reactive oxygen species-mediated mitochondrial damage, Free Radic. Biol. Med., 91, 264–274.
111. Yang, Y.J., Baek, J.Y., Goo, J., Shin, Y., Park, J.K., Jang, J.Y., Wang, S.B., Jeong, W., Lee, H.J., Um, H.-D., Lee, S.K., Choi, Y., Rhee, S.G., and Chang, T.-S. (2016) Effective killing of cancer cells through ROS-mediated mechanisms by AMRI-59 targeting peroxiredoxin I, Antioxid. Redox Signal., 24, 453–469.
112. Kim, T.H., Song, J., Kim, S.-H., Parikh, A.K., Mo, X., Palanichamy, K., Kaur, B., Yu, J., Yoon, S.O., Nakano, I., and Kwon, C.-H. (2014) Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells, Neuro. Oncol., 16, 1354–1364.
113. Jo, M., Yun, H.-M., Park, K.-R., Park, M.H., Lee, D.H., Cho, S.H., Yoo, H.-S., Lee, Y.-M., Jeong, H.S., Kim, Y., Jung, J.K., Hwang, B.Y., Lee, M.K., Kim, N.D., Han, S.B., and Hong, J.T. (2014) Anti-cancer effect of thiacremonone through down regulation of peroxiredoxin 6, PLoS One, 9, 1–10.
114. Lee, H.L., Park, M.H., Son, D.J., Song, H.S., Kim, J.H., Ko, S.C., Song, M.J., Lee, W.H., Yoon, J.H., Ham, Y.W., Han, S.B., and Hong, J.T. (2015) Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression, Oncotarget, 6, 22139–22151.
115. Marengo, B., Nitti, M., Furfaro, A.L., Colla, R., Ciucis, C. De, Marinari, U.M., Pronzato, M.A., Traverso, N., and Domenicotti, C. (2016) Redox homeostasis and cellular antioxidant systems: crucial players in cancer growth and therapy, Oxid. Med. Cell. Longev., 6235641.