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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Mini-Review Article

The Role of Peptidyl Arginine Deiminase IV(PADI4) in Cancers

Author(s): Xiangmei Wu, Yuji Wang and Wenjing Wang*

Volume 23, Issue 3, 2023

Published on: 25 August, 2022

Page: [256 - 265] Pages: 10

DOI: 10.2174/1871520622666220614115309

Price: $65

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Abstract

Background: Peptidyl arginine deiminase IV (PADI4, also called PAD4), a Ca2+-dependent posttranslational modification enzyme, catalyzes the conversion of arginine residues to non-coded citrulline residues. Dysregulation of PADI4 is involved in a variety of diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), Alzheimer's disease (AD) and many kinds of malignant tumors.

Objective: The roles of PADI4 in different tumors and the underlying molecular mechanisms are presented in this article.

Results: PADI4-mediated citrullination is associated with either transcriptional activation or repression in different contexts. Abnormal expression of PADI4 exists in a variety of malignant tumors and affects tumor progression and metastasis. Epithelial-to-mesenchymal transition (EMT), apoptosis, and neutrophil extracellular traps (NETs) may be the underlying molecular mechanisms.

Conclusion: PADI4 plays crucial role in the occurrence, development, and metastasis of tumors, and PADI4 may be an effective biomarker for cancer prognosis and a potential target for cancer treatment.

Keywords: PADI4, citrullination, cancer, EMT, NETs, apoptosis.

Graphical Abstract

[1]
Mondal, S.; Thompson, P.R. Protein Arginine Deiminases (PADs): Biochemistry and chemical biology of protein citrullination. Acc. Chem. Res., 2019, 52(3), 818-832.
[http://dx.doi.org/10.1021/acs.accounts.9b00024] [PMID: 30844238]
[2]
Vossenaar, E.R.; Zendman, A.J.; van Venrooij, W.J.; Pruijn, G.J. PAD, a growing family of citrullinating enzymes: Genes, features and involvement in disease. BioEssays, 2003, 25(11), 1106-1118.
[http://dx.doi.org/10.1002/bies.10357] [PMID: 14579251]
[3]
Yuzhalin, A.E. Citrullination in cancer. Cancer Res., 2019, 79(7), 1274-1284.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2797] [PMID: 30894374]
[4]
Zhang, Y.; Yang, Y.; Hu, X.; Wang, Z.; Li, L.; Chen, P. PADs in cancer: Current and future. Biochim. Biophys. Acta Rev. Cancer, 2021, 1875(1), 188492.
[http://dx.doi.org/10.1016/j.bbcan.2020.188492] [PMID: 33321174]
[5]
Nakashima, K.; Hagiwara, T.; Ishigami, A.; Nagata, S.; Asaga, H.; Kuramoto, M.; Senshu, T.; Yamada, M. Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3). J. Biol. Chem., 1999, 274(39), 27786-27792.
[http://dx.doi.org/10.1074/jbc.274.39.27786] [PMID: 10488123]
[6]
Nakashima, K.; Hagiwara, T.; Yamada, M. Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes. J. Biol. Chem., 2002, 277(51), 49562-49568.
[http://dx.doi.org/10.1074/jbc.M208795200] [PMID: 12393868]
[7]
Wang, Y.; Chen, R.; Gan, Y.; Ying, S. The roles of PAD2- and PAD4-mediated protein citrullination catalysis in cancers. Int. J. Cancer, 2021, 148(2), 267-276.
[http://dx.doi.org/10.1002/ijc.33205] [PMID: 33459350]
[8]
Darrah, E.; Andrade, F. Rheumatoid arthritis and citrullination. Curr. Opin. Rheumatol., 2018, 30(1), 72-78.
[http://dx.doi.org/10.1097/BOR.0000000000000452] [PMID: 28937414]
[9]
Kolarz, B.; Ciesla, M.; Dryglewska, M.; Majdan, M. Peptidyl arginine deiminase type 4 gene promoter hypo-methylation in rheumatoid arthritis. J. Clin. Med., 2020, 9(7), E2049.
[http://dx.doi.org/10.3390/jcm9072049] [PMID: 32629762]
[10]
Chang, X.; Fang, K. PADI4 and tumourigenesis. Cancer Cell Int., 2010, 10(1), 7.
[http://dx.doi.org/10.1186/1475-2867-10-7] [PMID: 20222985]
[11]
Jones, J.E.; Causey, C.P.; Knuckley, B.; Slack-Noyes, J.L.; Thompson, P.R. Protein arginine deiminase 4 (PAD4): Current understanding and future therapeutic potential. Curr. Opin. Drug Discov. Devel., 2009, 12(5), 616-627.
[PMID: 19736621]
[12]
Ramazi, S.; Allahverdi, A.; Zahiri, J. Evaluation of post-translational modifications in histone proteins: A review on histone modification defects in developmental and neurological disorders. J. Biosci., 2020, 45(1), 45.
[http://dx.doi.org/10.1007/s12038-020-00099-2] [PMID: 33184251]
[13]
Taylor, B.C.; Young, N.L. Combinations of histone post-translational modifications. Biochem. J., 2021, 478(3), 511-532.
[http://dx.doi.org/10.1042/BCJ20200170] [PMID: 33567070]
[14]
Tessarz, P.; Kouzarides, T. Histone core modifications regulating nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol., 2014, 15(11), 703-708.
[http://dx.doi.org/10.1038/nrm3890] [PMID: 25315270]
[15]
Tanikawa, C.; Ueda, K.; Suzuki, A.; Iida, A.; Nakamura, R.; Atsuta, N.; Tohnai, G.; Sobue, G.; Saichi, N.; Momozawa, Y.; Kamatani, Y.; Kubo, M.; Yamamoto, K.; Nakamura, Y.; Matsuda, K. Citrullination of RGG motifs in FET proteins by PAD4 regulates protein aggregation and ALS susceptibility. Cell Rep., 2018, 22(6), 1473-1483.
[http://dx.doi.org/10.1016/j.celrep.2018.01.031] [PMID: 29425503]
[16]
Fuhrmann, J.; Thompson, P.R. Protein arginine methylation and citrullination in epigenetic regulation. ACS Chem. Biol., 2016, 11(3), 654-668.
[http://dx.doi.org/10.1021/acschembio.5b00942] [PMID: 26686581]
[17]
Wang, Y.; Wysocka, J.; Sayegh, J.; Lee, Y.H.; Perlin, J.R.; Leonelli, L.; Sonbuchner, L.S.; McDonald, C.H.; Cook, R.G.; Dou, Y.; Roeder, R.G.; Clarke, S.; Stallcup, M.R.; Allis, C.D.; Coonrod, S.A. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science, 2004, 306(5694), 279-283.
[http://dx.doi.org/10.1126/science.1101400] [PMID: 15345777]
[18]
Raijmakers, R.; Zendman, A.J.; Egberts, W.V.; Vossenaar, E.R.; Raats, J.; Soede-Huijbregts, C.; Rutjes, F.P.; van Veelen, P.A.; Drijfhout, J.W.; Pruijn, G.J. Methylation of arginine residues interferes with citrullination by peptidylarginine deiminases in vitro. J. Mol. Biol., 2007, 367(4), 1118-1129.
[http://dx.doi.org/10.1016/j.jmb.2007.01.054] [PMID: 17303166]
[19]
Cuthbert, G.L.; Daujat, S.; Snowden, A.W.; Erdjument-Bromage, H.; Hagiwara, T.; Yamada, M.; Schneider, R.; Gregory, P.D.; Tempst, P.; Bannister, A.J.; Kouzarides, T. Histone deimination antagonizes arginine methylation. Cell, 2004, 118(5), 545-553.
[http://dx.doi.org/10.1016/j.cell.2004.08.020] [PMID: 15339660]
[20]
Zheng, Q.; Osunsade, A.; David, Y. Protein arginine deiminase 4 antagonizes methylglyoxal-induced histone glycation. Nat. Commun., 2020, 11(1), 3241.
[http://dx.doi.org/10.1038/s41467-020-17066-y] [PMID: 32591537]
[21]
Li, P.; Wang, D.; Yao, H.; Doret, P.; Hao, G.; Shen, Q.; Qiu, H.; Zhang, X.; Wang, Y.; Chen, G.; Wang, Y. Coordination of PAD4 and HDAC2 in the regulation of p53-target gene expression. Oncogene, 2010, 29(21), 3153-3162.
[http://dx.doi.org/10.1038/onc.2010.51] [PMID: 20190809]
[22]
Lee, C.Y.; Wang, D.; Wilhelm, M.; Zolg, D.P.; Schmidt, T.; Schnatbaum, K.; Reimer, U.; Pontén, F.; Uhlén, M.; Hahne, H.; Kuster, B. Mining the human tissue proteome for protein citrullination. Mol. Cell. Proteomics, 2018, 17(7), 1378-1391.
[http://dx.doi.org/10.1074/mcp.RA118.000696] [PMID: 29610271]
[23]
Mohanan, S.; Cherrington, B.D.; Horibata, S.; McElwee, J.L.; Thompson, P.R.; Coonrod, S.A. Potential role of peptidylarginine deiminase enzymes and protein citrullination in cancer pathogenesis. Biochem. Res. Int., 2012, 2012, 895343.
[http://dx.doi.org/10.1155/2012/895343] [PMID: 23019525]
[24]
Zhang, X.; Gamble, M.J.; Stadler, S.; Cherrington, B.D.; Causey, C.P.; Thompson, P.R.; Roberson, M.S.; Kraus, W.L.; Coonrod, S.A. Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells. PLoS Genet., 2011, 7(6), e1002112.
[http://dx.doi.org/10.1371/journal.pgen.1002112] [PMID: 21655091]
[25]
Li, Q.J.; Yang, S.H.; Maeda, Y.; Sladek, F.M.; Sharrocks, A.D.; Martins-Green, M. MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300. EMBO J., 2003, 22(2), 281-291.
[http://dx.doi.org/10.1093/emboj/cdg028] [PMID: 12514134]
[26]
Guo, Q.; Fast, W. Citrullination of inhibitor of growth 4 (ING4) by peptidylarginine deminase 4 (PAD4) disrupts the interaction between ING4 and p53. J. Biol. Chem., 2011, 286(19), 17069-17078.
[http://dx.doi.org/10.1074/jbc.M111.230961] [PMID: 21454715]
[27]
Deplus, R.; Denis, H.; Putmans, P.; Calonne, E.; Fourrez, M.; Yamamoto, K.; Suzuki, A.; Fuks, F. Citrullination of DNMT3A by PADI4 regulates its stability and controls DNA methylation. Nucleic Acids Res., 2014, 42(13), 8285-8296.
[http://dx.doi.org/10.1093/nar/gku522] [PMID: 24957603]
[28]
Chang, X.; Han, J. Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors. Mol. Carcinog., 2006, 45(3), 183-196.
[http://dx.doi.org/10.1002/mc.20169] [PMID: 16355400]
[29]
Wang, Y.; Lyu, Y.; Tu, K.; Xu, Q.; Yang, Y.; Salman, S.; Le, N.; Lu, H.; Chen, C.; Zhu, Y.; Wang, R.; Liu, Q.; Semenza, G.L. Histone citrullination by PADI4 is required for HIF-dependent transcriptional responses to hypoxia and tumor vascularization. Sci. Adv., 2021, 7(35), eabe3771.
[http://dx.doi.org/10.1126/sciadv.abe3771] [PMID: 34452909]
[30]
Chang, X.; Han, J.; Pang, L.; Zhao, Y.; Yang, Y.; Shen, Z. Increased PADI4 expression in blood and tissues of patients with malignant tumors. BMC Cancer, 2009, 9(1), 40.
[http://dx.doi.org/10.1186/1471-2407-9-40] [PMID: 19183436]
[31]
Shi, L.; Yao, H.; Liu, Z.; Xu, M.; Tsung, A.; Wang, Y. Endogenous PAD4 in breast cancer cells mediates cancer extracellular chromatin network formation and promotes lung metastasis. Mol. Cancer Res., 2020, 18(5), 735-747.
[http://dx.doi.org/10.1158/1541-7786.MCR-19-0018] [PMID: 32193354]
[32]
Wang, L.; Chang, X.; Yuan, G.; Zhao, Y.; Wang, P. Expression of peptidylarginine deiminase type 4 in ovarian tumors. Int. J. Biol. Sci., 2010, 6(5), 454-464.
[http://dx.doi.org/10.7150/ijbs.6.454] [PMID: 20827398]
[33]
Zhai, Q.; Qin, J.; Jin, X.; Sun, X.; Wang, L.; Du, W.; Li, T.; Xiang, X. PADI4 modulates the invasion and migration of osteosarcoma cells by down-regulation of epithelial-mesenchymal transition. Life Sci., 2020, 256, 117968.
[http://dx.doi.org/10.1016/j.lfs.2020.117968] [PMID: 32544462]
[34]
Yuzhalin, A.E.; Gordon-Weeks, A.N.; Tognoli, M.L.; Jones, K.; Markelc, B.; Konietzny, R.; Fischer, R.; Muth, A.; O’Neill, E.; Thompson, P.R.; Venables, P.J.; Kessler, B.M.; Lim, S.Y.; Muschel, R.J. Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix. Nat. Commun., 2018, 9(1), 4783.
[http://dx.doi.org/10.1038/s41467-018-07306-7] [PMID: 30429478]
[35]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[36]
Moshkovich, N.; Ochoa, H.J.; Tang, B.; Yang, H.H.; Yang, Y.; Huang, J.; Lee, M.P.; Wakefield, L.M. Peptidylarginine deiminase IV regulates breast cancer stem cells via a novel tumor cell-autonomous suppressor role. Cancer Res., 2020, 80(11), 2125-2137.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-3018] [PMID: 32265227]
[37]
Curtis, C.; Shah, S.P.; Chin, S.F.; Turashvili, G.; Rueda, O.M.; Dunning, M.J.; Speed, D.; Lynch, A.G.; Samarajiwa, S.; Yuan, Y.; Gräf, S.; Ha, G.; Haffari, G.; Bashashati, A.; Russell, R.; McKinney, S.; Langerød, A.; Green, A.; Provenzano, E.; Wishart, G.; Pinder, S.; Watson, P.; Markowetz, F.; Murphy, L.; Ellis, I.; Purushotham, A.; Børresen-Dale, A.L.; Brenton, J.D.; Tavaré, S.; Caldas, C.; Aparicio, S. The ge-nomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 2012, 486(7403), 346-352.
[http://dx.doi.org/10.1038/nature10983] [PMID: 22522925]
[38]
Neira, J.L.; Araujo-Abad, S.; Cámara-Artigas, A.; Rizzuti, B.; Abian, O.; Giudici, A.M.; Velazquez-Campoy, A.; de Juan Romero, C. Biochemical and biophysical characterization of PADI4 supports its involvement in cancer. Arch. Biochem. Biophys., 2022, 717, 109125.
[http://dx.doi.org/10.1016/j.abb.2022.109125] [PMID: 35081374]
[39]
Dong, S.; Zhang, Z.; Takahara, H. Estrogen-enhanced peptidylarginine deiminase type IV gene (PADI4) expression in MCF-7 cells is mediated by estrogen receptor-alpha-promoted transfactors activator protein-1, nuclear factor-Y, and Sp1. Mol. Endocrinol., 2007, 21(7), 1617-1629.
[http://dx.doi.org/10.1210/me.2006-0550] [PMID: 17456793]
[40]
Dongre, A.; Weinberg, R.A. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol., 2019, 20(2), 69-84.
[http://dx.doi.org/10.1038/s41580-018-0080-4] [PMID: 30459476]
[41]
Mittal, V. Epithelial mesenchymal transition in tumor metastasis. Annu. Rev. Pathol., 2018, 13(1), 395-412.
[http://dx.doi.org/10.1146/annurev-pathol-020117-043854] [PMID: 29414248]
[42]
Kim, B.N.; Ahn, D.H.; Kang, N.; Yeo, C.D.; Kim, Y.K.; Lee, K.Y.; Kim, T.J.; Lee, S.H.; Park, M.S.; Yim, H.W.; Park, J.Y.; Park, C.K.; Kim, S.J. TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci. Rep., 2020, 10(1), 10597.
[http://dx.doi.org/10.1038/s41598-020-67325-7] [PMID: 32606331]
[43]
Stadler, S.C.; Vincent, C.T.; Fedorov, V.D.; Patsialou, A.; Cherrington, B.D.; Wakshlag, J.J.; Mohanan, S.; Zee, B.M.; Zhang, X.; Garcia, B.A.; Condeelis, J.S.; Brown, A.M.; Coonrod, S.A.; Allis, C.D. Dysregulation of PAD4-mediated citrullination of nuclear GSK3β activates TGF-β signaling and induces epithelial-to-mesenchymal transition in breast cancer cells. Proc. Natl. Acad. Sci. USA, 2013, 110(29), 11851-11856.
[http://dx.doi.org/10.1073/pnas.1308362110] [PMID: 23818587]
[44]
Zhu, X.; Chen, L.; Liu, L.; Niu, X. EMT-Mediated acquired EGFR-TKI resistance in NSCLC: Mechanisms and strategies. Front. Oncol., 2019, 9, 1044.
[http://dx.doi.org/10.3389/fonc.2019.01044] [PMID: 31681582]
[45]
Duan, Q.; Pang, C.; Chang, N.; Zhang, J.; Liu, W. Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition. Oncol. Rep., 2016, 36(1), 551-558.
[http://dx.doi.org/10.3892/or.2016.4780] [PMID: 27176594]
[46]
Liu, M.; Qu, Y.; Teng, X.; Xing, Y.; Li, D.; Li, C.; Cai, L. PADI4-mediated epithelial-mesenchymal transition in lung cancer cells. Mol. Med. Rep., 2019, 19(4), 3087-3094.
[http://dx.doi.org/10.3892/mmr.2019.9968] [PMID: 30816464]
[47]
Yaacoub, K.; Pedeux, R.; Tarte, K.; Guillaudeux, T. Role of the tumor microenvironment in regulating apoptosis and cancer progression. Cancer Lett., 2016, 378(2), 150-159.
[http://dx.doi.org/10.1016/j.canlet.2016.05.012] [PMID: 27224890]
[48]
Fan, L.; Zong, M.; Gong, R.; He, D.; Li, N.; Sun, L.S.; Ye, Q.; Yu, S. PADI4 epigenetically suppresses p21 transcription and inhibits cell apoptosis in fibroblast-like synoviocytes from rheumatoid arthritis patients. Int. J. Biol. Sci., 2017, 13(3), 358-366.
[http://dx.doi.org/10.7150/ijbs.16879] [PMID: 28367100]
[49]
Fan, T.; Zhang, C.; Zong, M.; Fan, L. Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibro-blast-like synoviocytes in rheumatoid arthritis. Mol. Med. Rep., 2018, 17(4), 5116-5124.
[http://dx.doi.org/10.3892/mmr.2018.8501] [PMID: 29393388]
[50]
Eriksson, S.E.; Ceder, S.; Bykov, V.J.N.; Wiman, K.G. p53 as a hub in cellular redox regulation and therapeutic target in cancer. J. Mol. Cell Biol., 2019, 11(4), 330-341.
[http://dx.doi.org/10.1093/jmcb/mjz005] [PMID: 30892598]
[51]
Roszkowska, K.A.; Gizinski, S.; Sady, M.; Gajewski, Z.; Olszewski, M.B. Gain-of-function mutations in p53 in cancer invasiveness and metastasis. Int. J. Mol. Sci., 2020, 21(4), E1334.
[http://dx.doi.org/10.3390/ijms21041334] [PMID: 32079237]
[52]
Li, P.; Yao, H.; Zhang, Z.; Li, M.; Luo, Y.; Thompson, P.R.; Gilmour, D.S.; Wang, Y. Regulation of p53 target gene expression by peptidylarginine deiminase 4. Mol. Cell. Biol., 2008, 28(15), 4745-4758.
[http://dx.doi.org/10.1128/MCB.01747-07] [PMID: 18505818]
[53]
Mirza, A.; Wu, Q.; Wang, L.; McClanahan, T.; Bishop, W.R.; Gheyas, F.; Ding, W.; Hutchins, B.; Hockenberry, T.; Kirschmeier, P.; Greene, J.R.; Liu, S. Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression. Oncogene, 2003, 22(23), 3645-3654.
[http://dx.doi.org/10.1038/sj.onc.1206477] [PMID: 12789273]
[54]
Tanikawa, C.; Ueda, K.; Nakagawa, H.; Yoshida, N.; Nakamura, Y.; Matsuda, K. Regulation of protein Citrullination through p53/PADI4 network in DNA damage response. Cancer Res., 2009, 69(22), 8761-8769.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2280] [PMID: 19843866]
[55]
Liu, G.Y.; Liao, Y.F.; Chang, W.H.; Liu, C.C.; Hsieh, M.C.; Hsu, P.C.; Tsay, G.J.; Hung, H.C. Overexpression of peptidylarginine deiminase IV features in apoptosis of haematopoietic cells. Apoptosis, 2006, 11(2), 183-196.
[http://dx.doi.org/10.1007/s10495-006-3715-4] [PMID: 16502257]
[56]
Zhai, Q.; Wang, L.; Zhao, P.; Li, T. Role of citrullination modification catalyzed by peptidylarginine deiminase 4 in gene transcriptional regulation. Acta Biochim. Biophys. Sin. (Shanghai), 2017, 49(7), 567-572.
[http://dx.doi.org/10.1093/abbs/gmx042] [PMID: 28472221]
[57]
Tanikawa, C.; Espinosa, M.; Suzuki, A.; Masuda, K.; Yamamoto, K.; Tsuchiya, E.; Ueda, K.; Daigo, Y.; Nakamura, Y.; Matsuda, K. Regulation of histone modification and chromatin structure by the p53-PADI4 pathway. Nat. Commun., 2012, 3(1), 676.
[http://dx.doi.org/10.1038/ncomms1676] [PMID: 22334079]
[58]
Leshner, M.; Wang, S.; Lewis, C.; Zheng, H.; Chen, X.A.; Santy, L.; Wang, Y. PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures. Front. Immunol., 2012, 3, 307.
[http://dx.doi.org/10.3389/fimmu.2012.00307] [PMID: 23060885]
[59]
Zhou, Q.; Song, C.; Liu, X.; Qin, H.; Miao, L.; Zhang, X. Peptidylarginine deiminase 4 overexpression resensitizes MCF-7/ADR breast cancer cells to adriamycin via GSK3β/p53 activation. Cancer Manag. Res., 2019, 11, 625-636.
[http://dx.doi.org/10.2147/CMAR.S191353] [PMID: 30666159]
[60]
Brosh, R.; Assia-Alroy, Y.; Molchadsky, A.; Bornstein, C.; Dekel, E.; Madar, S.; Shetzer, Y.; Rivlin, N.; Goldfinger, N.; Sarig, R.; Rotter, V. p53 counteracts reprogramming by inhibiting mesenchymal-to-epithelial transition. Cell Death Differ., 2013, 20(2), 312-320.
[http://dx.doi.org/10.1038/cdd.2012.125] [PMID: 22996684]
[61]
Yao, H.; Li, P.; Venters, B.J.; Zheng, S.; Thompson, P.R.; Pugh, B.F.; Wang, Y. Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis. J. Biol. Chem., 2008, 283(29), 20060-20068.
[http://dx.doi.org/10.1074/jbc.M802940200] [PMID: 18499678]
[62]
Brinkmann, V. Neutrophil extracellular traps in the second decade. J. Innate Immun., 2018, 10(5-6), 414-421.
[http://dx.doi.org/10.1159/000489829] [PMID: 29909412]
[63]
Papayannopoulos, V. Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol., 2018, 18(2), 134-147.
[http://dx.doi.org/10.1038/nri.2017.105] [PMID: 28990587]
[64]
Wang, Y.; Li, M.; Stadler, S.; Correll, S.; Li, P.; Wang, D.; Hayama, R.; Leonelli, L.; Han, H.; Grigoryev, S.A.; Allis, C.D.; Coonrod, S.A. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J. Cell Biol., 2009, 184(2), 205-213.
[http://dx.doi.org/10.1083/jcb.200806072] [PMID: 19153223]
[65]
Kuczia, P.; Zuk, J.; Iwaniec, T.; Soja, J.; Dropinski, J.; Malesa-Wlodzik, M.; Zareba, L.; Bazan, J.G.; Undas, A.; Bazan-Socha, S. Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients. Clin. Transl. Allergy, 2020, 10(1), 31.
[http://dx.doi.org/10.1186/s13601-020-00337-8] [PMID: 32685129]
[66]
Thålin, C.; Lundström, S.; Seignez, C.; Daleskog, M.; Lundström, A.; Henriksson, P.; Helleday, T.; Phillipson, M.; Wallén, H.; Demers, M. Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer. PLoS One, 2018, 13(1), e0191231.
[http://dx.doi.org/10.1371/journal.pone.0191231] [PMID: 29324871]
[67]
Masucci, M.T.; Minopoli, M.; Del Vecchio, S.; Carriero, M.V. The emerging role of Neutrophil Extracellular Traps (NETs) in tumor progression and metastasis. Front. Immunol., 2020, 11, 1749.
[http://dx.doi.org/10.3389/fimmu.2020.01749] [PMID: 33042107]
[68]
Wang, W.; Zhang, J.; Zheng, N.; Li, L.; Wang, X.; Zeng, Y. The role of neutrophil extracellular traps in cancer metastasis. Clin. Transl. Med., 2020, 10(6), e126.
[http://dx.doi.org/10.1002/ctm2.126] [PMID: 32961033]
[69]
Munir, H.; Jones, J.O.; Janowitz, T.; Hoffmann, M.; Euler, M.; Martins, C.P.; Welsh, S.J.; Shields, J.D. Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth. Nat. Commun., 2021, 12(1), 683.
[http://dx.doi.org/10.1038/s41467-021-20982-2] [PMID: 33514748]
[70]
Muqaku, B.; Pils, D.; Mader, J.C.; Aust, S.; Mangold, A.; Muqaku, L.; Slany, A.; Del Favero, G.; Gerner, C. Neutrophil extracellular trap formation correlates with favorable overall survival in high grade ovarian cancer. Cancers (Basel), 2020, 12(2), E505.
[http://dx.doi.org/10.3390/cancers12020505] [PMID: 32098278]
[71]
Oklu, R.; Sheth, R.A.; Wong, K.H.K.; Jahromi, A.H.; Albadawi, H. Neutrophil extracellular traps are increased in cancer patients but does not associate with venous thrombosis. Cardiovasc. Diagn. Ther., 2017, 7(S3)(Suppl. 3), S140-S149.
[http://dx.doi.org/10.21037/cdt.2017.08.01] [PMID: 29399517]
[72]
Zhang, Y.; Hu, Y.; Ma, C.; Sun, H.; Wei, X.; Li, M.; Wei, W.; Zhang, F.; Yang, F.; Wang, H.; Gu, K. Diagnostic, therapeutic predictive, and prognostic value of neutrophil extracellular traps in patients with gastric adenocarcinoma. Front. Oncol., 2020, 10, 1036.
[http://dx.doi.org/10.3389/fonc.2020.01036] [PMID: 32714865]
[73]
Tohme, S.; Yazdani, H.O.; Al-Khafaji, A.B.; Chidi, A.P.; Loughran, P.; Mowen, K.; Wang, Y.; Simmons, R.L.; Huang, H.; Tsung, A. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical Stress. Cancer Res., 2016, 76(6), 1367-1380.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1591] [PMID: 26759232]
[74]
Onuma, A.E.; Zhang, H.; Gil, L.; Huang, H.; Tsung, A. Surgical stress promotes tumor progression: A focus on the impact of the immune response. J. Clin. Med., 2020, 9(12), E4096.
[http://dx.doi.org/10.3390/jcm9124096] [PMID: 33353113]
[75]
Cools-Lartigue, J.; Spicer, J.; McDonald, B.; Gowing, S.; Chow, S.; Giannias, B.; Bourdeau, F.; Kubes, P.; Ferri, L. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J. Clin. Invest., 2013, 123(8), 67484.
[http://dx.doi.org/10.1172/JCI67484] [PMID: 23863628]
[76]
Najmeh, S.; Cools-Lartigue, J.; Rayes, R.F.; Gowing, S.; Vourtzoumis, P.; Bourdeau, F.; Giannias, B.; Berube, J.; Rousseau, S.; Ferri, L.E.; Spicer, J.D. Neutrophil extracellular traps sequester circulating tumor cells via β1-integrin mediated interactions. Int. J. Cancer, 2017, 140(10), 2321-2330.
[http://dx.doi.org/10.1002/ijc.30635] [PMID: 28177522]
[77]
Monti, M.; De Rosa, V.; Iommelli, F.; Carriero, M.V.; Terlizzi, C.; Camerlingo, R.; Belli, S.; Fonti, R.; Di Minno, G.; Del Vecchio, S. Neutrophil extracellular traps as an adhesion substrate for different tumor cells expressing RGD-binding integrins. Int. J. Mol. Sci., 2018, 19(8), E2350.
[http://dx.doi.org/10.3390/ijms19082350] [PMID: 30096958]
[78]
Martins-Cardoso, K.; Almeida, V.H.; Bagri, K.M.; Rossi, M.I.D.; Mermelstein, C.S.; König, S.; Monteiro, R.Q. Neutrophil Extracellular Traps (NETs) promote pro-metastatic phenotype in human breast cancer cells through Epithelial-Mesenchymal transition. Cancers (Basel), 2020, 12(6), E1542.
[http://dx.doi.org/10.3390/cancers12061542] [PMID: 32545405]
[79]
Miller-Ocuin, J.L.; Liang, X.; Boone, B.A.; Doerfler, W.R.; Singhi, A.D.; Tang, D.; Kang, R.; Lotze, M.T.; Zeh, H.J., III DNA released from neutrophil extracellular traps (NETs) activates pancreatic stellate cells and enhances pancreatic tumor growth. OncoImmunology, 2019, 8(9), e1605822.
[http://dx.doi.org/10.1080/2162402X.2019.1605822] [PMID: 31428515]
[80]
Chang, X.T.; Wu, H.; Li, H.L.; Li, H.L.; Zheng, Y.B. PADI4 promotes epithelial-mesenchymal transition(EMT) in gastric cancer via the upregulation of interleukin 8. BMC Gastroenterol., 2022, 22(1), 25.
[http://dx.doi.org/10.1186/s12876-022-02097-0] [PMID: 35045833]
[81]
Teijeira, A.; Garasa, S.; Ochoa, M.C.; Villalba, M.; Olivera, I.; Cirella, A.; Eguren-Santamaria, I.; Berraondo, P.; Schalper, K.A.; de Andrea, C.E.; Sanmamed, M.F.; Melero, I. IL8, neutrophils, and NETs in a collusion against cancer immunity and immunotherapy. Clin. Cancer Res., 2021, 27(9), 2383-2393.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-1319] [PMID: 33376096]
[82]
Zha, C.; Meng, X.; Li, L.; Mi, S.; Qian, D.; Li, Z.; Wu, P.; Hu, S.; Zhao, S.; Cai, J.; Liu, Y. Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis. Cancer Biol. Med., 2020, 17(1), 154-168.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0353] [PMID: 32296583]
[83]
Yang, L.; Liu, L.; Zhang, R.; Hong, J.; Wang, Y.; Wang, J.; Zuo, J.; Zhang, J.; Chen, J.; Hao, H. IL-8 mediates a positive loop connecting increased neutrophil extracellular traps (NETs) and colorectal cancer liver metastasis. J. Cancer, 2020, 11(15), 4384-4396.
[http://dx.doi.org/10.7150/jca.44215] [PMID: 32489457]
[84]
Albrengues, J.; Shields, M.A.; Ng, D.; Park, C.G.; Ambrico, A.; Poindexter, M.E.; Upadhyay, P.; Uyeminami, D.L.; Pommier, A.; Küttner, V.; Bružas, E.; Maiorino, L.; Bautista, C.; Carmona, E.M.; Gimotty, P.A.; Fearon, D.T.; Chang, K.; Lyons, S.K.; Pinkerton, K.E.; Trotman, L.C.; Goldberg, M.S.; Yeh, J.T.; Egeblad, M. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science, 2018, 361(6409), eaao4227.
[http://dx.doi.org/10.1126/science.aao4227] [PMID: 30262472]
[85]
Yazdani, H.O.; Roy, E.; Comerci, A.J.; van der Windt, D.J.; Zhang, H.; Huang, H.; Loughran, P.; Shiva, S.; Geller, D.A.; Bartlett, D.L.; Tsung, A.; Sheng, T.; Simmons, R.L.; Tohme, S. Neutrophil extracellular traps drive mitochondrial homeostasis in tumors to augment growth. Cancer Res., 2019, 79(21), 5626-5639.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-0800] [PMID: 31519688]
[86]
Leal, A.C.; Mizurini, D.M.; Gomes, T.; Rochael, N.C.; Saraiva, E.M.; Dias, M.S.; Werneck, C.C.; Sielski, M.S.; Vicente, C.P.; Monteiro, R.Q. Tumor-derived exosomes induce the formation of neutrophil extracellular traps: Implications for the establishment of cancer-associated thrombosis. Sci. Rep., 2017, 7(1), 6438.
[http://dx.doi.org/10.1038/s41598-017-06893-7] [PMID: 28743887]
[87]
Jung, H.S.; Gu, J.; Kim, J.E.; Nam, Y.; Song, J.W.; Kim, H.K. Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression. PLoS One, 2019, 14(4), e0216055.
[http://dx.doi.org/10.1371/journal.pone.0216055] [PMID: 31034495]
[88]
Seo, J.D.; Gu, J.Y.; Jung, H.S.; Kim, Y.J.; Kim, H.K. Contact system activation and neutrophil extracellular trap markers: Risk factors for portal vein thrombosis in patients with hepatocellular carcinoma. Clin. Appl. Thromb. Hemost., 2019, 25, 1076029618825310.
[http://dx.doi.org/10.1177/1076029618825310] [PMID: 30808222]
[89]
Liu, Y.; Liu, L. The pro-tumor effect and the anti-tumor effect of neutrophils extracellular traps. Biosci. Trends, 2020, 13(6), 469-475.
[http://dx.doi.org/10.5582/bst.2019.01326] [PMID: 31866615]
[90]
Metzler, K.D.; Fuchs, T.A.; Nauseef, W.M.; Reumaux, D.; Roesler, J.; Schulze, I.; Wahn, V.; Papayannopoulos, V.; Zychlinsky, A. Myeloperoxidase is required for neutrophil extracellular trap formation: Implications for innate immunity. Blood, 2011, 117(3), 953-959.
[http://dx.doi.org/10.1182/blood-2010-06-290171] [PMID: 20974672]
[91]
Schedel, F.; Mayer-Hain, S.; Pappelbaum, K.I.; Metze, D.; Stock, M.; Goerge, T.; Loser, K.; Sunderkötter, C.; Luger, T.A.; Weishaupt, C. Evidence and impact of neutrophil extracellular traps in malignant melanoma. Pigment Cell Melanoma Res., 2020, 33(1), 63-73.
[http://dx.doi.org/10.1111/pcmr.12818] [PMID: 31402559]
[92]
Slade, D.J.; Subramanian, V.; Thompson, P.R. Pluripotency: Citrullination unravels stem cells. Nat. Chem. Biol., 2014, 10(5), 327-328.
[http://dx.doi.org/10.1038/nchembio.1504] [PMID: 24743255]
[93]
Christophorou, M.A.; Castelo-Branco, G.; Halley-Stott, R.P.; Oliveira, C.S.; Loos, R.; Radzisheuskaya, A.; Mowen, K.A.; Bertone, P.; Silva, J.C.; Zernicka-Goetz, M.; Nielsen, M.L.; Gurdon, J.B.; Kouzarides, T. Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature, 2014, 507(7490), 104-108.
[http://dx.doi.org/10.1038/nature12942] [PMID: 24463520]
[94]
Marzagalli, M.; Fontana, F.; Raimondi, M.; Limonta, P. Cancer stem cells-key players in tumor relapse. Cancers (Basel), 2021, 13(3), 376.
[http://dx.doi.org/10.3390/cancers13030376] [PMID: 33498502]
[95]
Mukha, A.; Dubrovska, A. Metabolic targeting of cancer stem cells. Front. Oncol., 2020, 10, 537930.
[http://dx.doi.org/10.3389/fonc.2020.537930] [PMID: 33415069]
[96]
Ravanan, P.; Srikumar, I.F.; Talwar, P. Autophagy: The spotlight for cellular stress responses. Life Sci., 2017, 188, 53-67.
[http://dx.doi.org/10.1016/j.lfs.2017.08.029] [PMID: 28866100]
[97]
Fader, C.M.; Sánchez, D.; Furlán, M.; Colombo, M.I. Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells. Traffic, 2008, 9(2), 230-250.
[http://dx.doi.org/10.1111/j.1600-0854.2007.00677.x] [PMID: 17999726]
[98]
Fan, T.; Zhang, C.; Zong, M.; Zhao, Q.; Yang, X.; Hao, C.; Zhang, H.; Yu, S.; Guo, J.; Gong, R.; Fan, S.; Wei, L.; Fan, L. Peptidylarginine deiminase IV promotes the development of chemoresistance through inducing autophagy in hepatocellular carcinoma. Cell Biosci., 2014, 4(1), 49.
[http://dx.doi.org/10.1186/2045-3701-4-49] [PMID: 25922661]
[99]
Nguyen, H.; James, E.A. Immune recognition of citrullinated epitopes. Immunology, 2016, 149(2), 131-138.
[http://dx.doi.org/10.1111/imm.12640] [PMID: 27531825]
[100]
Brentville, V.A.; Vankemmelbeke, M.; Metheringham, R.L.; Durrant, L.G. Post-translational modifications such as citrullination are excellent targets for cancer therapy. Semin. Immunol., 2020, 47, 101393.
[http://dx.doi.org/10.1016/j.smim.2020.101393] [PMID: 31932199]
[101]
Ireland, J.M.; Unanue, E.R. Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells. J. Exp. Med., 2011, 208(13), 2625-2632.
[http://dx.doi.org/10.1084/jem.20110640] [PMID: 22162830]
[102]
Brentville, V.A.; Metheringham, R.L.; Gunn, B.; Symonds, P.; Daniels, I.; Gijon, M.; Cook, K.; Xue, W.; Durrant, L.G. Citrullinated vimentin presented on MHC-II in tumor cells is a target for CD4+ T-Cell-mediated antitumor immunity. Cancer Res., 2016, 76(3), 548-560.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1085] [PMID: 26719533]
[103]
Durrant, L.G.; Metheringham, R.L.; Brentville, V.A. Autophagy, citrullination and cancer. Autophagy, 2016, 12(6), 1055-1056.
[http://dx.doi.org/10.1080/15548627.2016.1166326] [PMID: 27145231]
[104]
Fu, Q.F.; Liu, Y.; Fan, Y.; Hua, S.N.; Qu, H.Y.; Dong, S.W.; Li, R.L.; Zhao, M.Y.; Zhen, Y.; Yu, X.L.; Chen, Y.Y.; Luo, R.C.; Li, R.; Li, L.B.; Deng, X.J.; Fang, W.Y.; Liu, Z.; Song, X. Alphaenolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway. J. Hematol. Oncol., 2015, 8(1), 22.
[http://dx.doi.org/10.1186/s13045-015-0117-5] [PMID: 25887760]
[105]
Cook, K.; Daniels, I.; Symonds, P.; Pitt, T.; Gijon, M.; Xue, W.; Metheringham, R.; Durrant, L.; Brentville, V. Citrullinated α-enolase is an effective target for anti-cancer immunity. OncoImmunology, 2017, 7(2), e1390642.
[http://dx.doi.org/10.1080/2162402X.2017.1390642] [PMID: 29308319]
[106]
Brentville, V.A.; Metheringham, R.L.; Daniels, I.; Atabani, S.; Symonds, P.; Cook, K.W.; Vankemmelbeke, M.; Choudhury, R.; Vaghela, P.; Gijon, M.; Meiners, G.; Krebber, W.J.; Melief, C.J.M.; Durrant, L.G. Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses. J. Immunother. Cancer, 2020, 8(1), e000560.
[http://dx.doi.org/10.1136/jitc-2020-000560] [PMID: 32561639]
[107]
Slack, J.L.; Causey, C.P.; Thompson, P.R. Protein arginine deiminase 4: A target for an epigenetic cancer therapy. Cell. Mol. Life Sci., 2011, 68(4), 709-720.
[http://dx.doi.org/10.1007/s00018-010-0480-x] [PMID: 20706768]
[108]
Li, M.; Lin, C.; Deng, H.; Strnad, J.; Bernabei, L.; Vogl, D.T.; Burke, J.J.; Nefedova, Y. A novel peptidylarginine deiminase 4 (PAD4) inhibitor BMS-P5 Blocks formation of neutrophil extracellular traps and delays progression of multiple myeloma. Mol. Cancer Ther., 2020, 19(7), 1530-1538.
[http://dx.doi.org/10.1158/1535-7163.MCT-19-1020] [PMID: 32371579]
[109]
Dreyton, C.J.; Anderson, E.D.; Subramanian, V.; Boger, D.L.; Thompson, P.R. Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation. Bioorg. Med. Chem., 2014, 22(4), 1362-1369.
[http://dx.doi.org/10.1016/j.bmc.2013.12.064] [PMID: 24440480]
[110]
Wei, L.; Wang, X.; Luo, M.; Wang, H.; Chen, H.; Huang, C. The PAD4 inhibitor GSK484 enhances the radiosensitivity of triple-negative breast cancer. Hum. Exp. Toxicol., 2021, 40(7), 1074-1083.
[http://dx.doi.org/10.1177/0960327120979028] [PMID: 33355008]
[111]
Wang, Y.; Li, P.; Wang, S.; Hu, J.; Chen, X.A.; Wu, J.; Fisher, M.; Oshaben, K.; Zhao, N.; Gu, Y.; Wang, D.; Chen, G.; Wang, Y. Anti-cancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activity. J. Biol. Chem., 2012, 287(31), 25941-25953.
[http://dx.doi.org/10.1074/jbc.M112.375725] [PMID: 22605338]
[112]
Zhu, D.; Lu, Y.; Gui, L.; Wang, W.; Hu, X.; Chen, S.; Wang, Y.; Wang, Y. Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment. Acta Pharm. Sin. B, 2022, 12(15), 2592-2608.
[http://dx.doi.org/10.1016/j.apsb.2021.11.006]
[113]
Jones, J.E.; Slack, J.L.; Fang, P.; Zhang, X.; Subramanian, V.; Causey, C.P.; Coonrod, S.A.; Guo, M.; Thompson, P.R. Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors. ACS Chem. Biol., 2012, 7(1), 160-165.
[http://dx.doi.org/10.1021/cb200258q] [PMID: 22004374]
[114]
Bishayee, A.; Block, K. A broad-spectrum integrative design for cancer prevention and therapy: The challenge ahead. Semin. Cancer Biol., 2015, 35(Suppl.), S1-S4.
[http://dx.doi.org/10.1016/j.semcancer.2015.08.002] [PMID: 26260004]

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