Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

Neuronatin Promotes the Progression of Non-small Cell Lung Cancer by Activating the NF-κB Signaling

Author(s): Huanwen Xiong, Guohua Chen, Ke Fang, Weiguo Gu and Feng Qiu*

Volume 24, Issue 11, 2024

Published on: 30 January, 2024

Page: [1128 - 1143] Pages: 16

DOI: 10.2174/0115680096271746240103063325

Abstract

Background and Objectives: Understanding the regulatory mechanisms involving neuronatin (NNAT) in non-small cell lung cancer (NSCLC) is an ongoing challenge. This study aimed to elucidate the impact of NNAT knockdown on NSCLC by employing both in vitro and in vivo approaches.

Methods: To investigate the role of NNAT, its expression was silenced in NSCLC cell lines A549 and H226. Subsequently, various parameters, including cell proliferation, invasion, migration, and apoptosis, were assessed. Additionally, cell-derived xenograft models were established to evaluate the effect of NNAT knockdown on tumor growth. The expression of key molecules, including cyclin D1, B-cell leukemia/lymphoma 2 (Bcl-2), p65, matrix metalloproteinase (MMP) 2, and nerve growth factor (NGF) were examined both in vitro and in vivo. Nerve fiber density within tumor tissues was analyzed using silver staining.

Results: Upon NNAT knockdown, a remarkable reduction in NSCLC cell proliferation, invasion, and migration was observed, accompanied by elevated levels of apoptosis. Furthermore, the expression of cyclin D1, Bcl-2, MMP2, and phosphorylated p65 (p-p65) showed significant downregulation. In vivo, NNAT knockdown led to substantial inhibition of tumor growth and a concurrent decrease in cyclinD1, Bcl-2, MMP2, and p-p65 expression within tumor tissues. Importantly, NNAT knockdown also led to a decrease in nerve fiber density and downregulation of NGF expression within the xenograft tumor tissues.

Conclusion: Collectively, these findings suggest that neuronatin plays a pivotal role in driving NSCLC progression, potentially through the activation of the nuclear factor-kappa B signaling cascade. Additionally, neuronatin may contribute to the modulation of tumor microenvironment innervation in NSCLC. Targeting neuronatin inhibition emerges as a promising strategy for potential anti-NSCLC therapeutic intervention.

Graphical Abstract

[1]
Thai, A.A.; Solomon, B.J.; Sequist, L.V.; Gainor, J.F.; Heist, R.S. Lung cancer. Lancet, 2021, 398(10299), 535-554.
[http://dx.doi.org/10.1016/S0140-6736(21)00312-3] [PMID: 34273294]
[2]
Melosky, B.; Wheatley-Price, P.; Juergens, R.A.; Sacher, A.; Leighl, N.B.; Tsao, M.S.; Cheema, P.; Snow, S.; Liu, G.; Card, P.B.; Chu, Q. The rapidly evolving landscape of novel targeted therapies in advanced non-small cell lung cancer. Lung Cancer, 2021, 160, 136-151.
[http://dx.doi.org/10.1016/j.lungcan.2021.06.002] [PMID: 34353680]
[3]
Reck, M.; Remon, J.; Hellmann, M.D. First-line immunotherapy for non-small cell lung cancer. J. Clin. Oncol., 2022, 40(6), 586-597.
[http://dx.doi.org/10.1200/JCO.21.01497] [PMID: 34985920]
[4]
Allemani, C.; Matsuda, T.; Di Carlo, V.; Harewood, R.; Matz, M.; Nikšić, M.; Bonaventure, A.; Valkov, M.; Johnson, C.J.; Estève, J.; Ogunbiyi, O.J.; Azevedo e Silva, G.; Chen, W.Q.; Eser, S.; Engholm, G.; Stiller, C.A.; Monnereau, A.; Woods, R.R.; Visser, O.; Lim, G.H.; Aitken, J.; Weir, H.K.; Coleman, M.P.; Bouzbid, S.; Hamdi-Chérif, M.; Zaidi, Z.; Meguenni, K.; Regagba, D.; Bayo, S.; Cheick Bougadari, T.; Manraj, S.S.; Bendahhou, K.; Fabowale, A.; Bradshaw, D.; Somdyala, N.I.M.; Kumcher, I.; Moreno, F.; Calabrano, G.H.; Espinola, S.B.; Carballo Quintero, B.; Fita, R.; Diumenjo, M.C.; Laspada, W.D.; Ibañez, S.G.; Lima, C.A.; De Souza, P.C.F.; Del Pino, K.; Laporte, C.; Curado, M.P.; de Oliveira, J.C.; Veneziano, C.L.A.; Veneziano, D.B.; Latorre, M.R.D.O.; Tanaka, L.F.; Rebelo, M.S.; Santos, M.O.; Galaz, J.C.; Aparicio Aravena, M.; Sanhueza Monsalve, J.; Herrmann, D.A.; Vargas, S.; Herrera, V.M.; Uribe, C.J.; Bravo, L.E.; Garcia, L.S.; Arias-Ortiz, N.E.; Morantes, D.; Jurado, D.M.; Yépez Chamorro, M.C.; Delgado, S.; Ramirez, M.; Galán Alvarez, Y.H.; Torres, P.; Martínez-Reyes, F.; Jaramillo, L.; Quinto, R.; Castillo, J.; Mendoza, M.; Cueva, P.; Yépez, J.G.; Bhakkan, B.; Deloumeaux, J.; Joachim, C.; Macni, J.; Carrillo, R.; Shalkow Klincovstein, J.; Rivera Gomez, R.; Poquioma, E.; Tortolero-Luna, G.; Zavala, D.; Alonso, R.; Barrios, E.; Eckstrand, A.; Nikiforuk, C.; Noonan, G.; Turner, D.; Kumar, E.; Zhang, B.; McCrate, F.R.; Ryan, S.; MacIntyre, M.; Saint-Jacques, N.; Nishri, D.E.; McClure, C.A.; Vriends, K.A.; Kozie, S.; Stuart-Panko, H.; Freeman, T.; George, J.T.; Brockhouse, J.T.; O’Brien, D.K.; Holt, A.; Almon, L.; Kwong, S.; Morris, C.; Rycroft, R.; Mueller, L.; Phillips, C.E.; Brown, H.; Cromartie, B.; Schwartz, A.G.; Vigneau, F.; Levin, G.M.; Wohler, B.; Bayakly, R.; Ward, K.C.; Gomez, S.L.; McKinley, M.; Cress, R.; Green, M.D.; Miyagi, K.; Ruppert, L.P.; Lynch, C.F.; Huang, B.; Tucker, T.C.; Deapen, D.; Liu, L.; Hsieh, M.C.; Wu, X.C.; Schwenn, M.; Gershman, S.T.; Knowlton, R.C.; Alverson, G.; Copeland, G.E.; Bushhouse, S.; Rogers, D.B.; Jackson-Thompson, J.; Lemons, D.; Zimmerman, H.J.; Hood, M.; Roberts-Johnson, J.; Rees, J.R.; Riddle, B.; Pawlish, K.S.; Stroup, A.; Key, C.; Wiggins, C.; Kahn, A.R.; Schymura, M.J.; Radhakrishnan, S.; Rao, C.; Giljahn, L.K.; Slocumb, R.M.; Espinoza, R.E.; Khan, F.; Aird, K.G.; Beran, T.; Rubertone, J.J.; Slack, S.J.; Garcia, L.; Rousseau, D.L.; Janes, T.A.; Schwartz, S.M.; Bolick, S.W.; Hurley, D.M.; Whiteside, M.A.; Miller-Gianturco, P.; Williams, M.A.; Herget, K.; Sweeney, C.; Johnson, A.T.; Keitheri Cheteri, M.B.; Migliore Santiago, P.; Blankenship, S.E.; Farley, S.; Borchers, R.; Malicki, R.; Espinoza, J.R.; Grandpre, J.; Wilson, R.; Edwards, B.K.; Mariotto, A.; Lei, Y.; Wang, N.; Chen, J.S.; Zhou, Y.; He, Y.T.; Song, G.H.; Gu, X.P.; Mei, D.; Mu, H.J.; Ge, H.M.; Wu, T.H.; Li, Y.Y.; Zhao, D.L.; Jin, F.; Zhang, J.H.; Zhu, F.D.; Junhua, Q.; Yang, Y.L.; Jiang, C.X.; Biao, W.; Wang, J.; Li, Q.L.; Yi, H.; Zhou, X.; Dong, J.; Li, W.; Fu, F.X.; Liu, S.Z.; Chen, J.G.; Zhu, J.; Li, Y.H.; Lu, Y.Q.; Fan, M.; Huang, S.Q.; Guo, G.P.; Zhaolai, H.; Wei, K.; Zeng, H.; Demetriou, A.V.; Mang, W.K.; Ngan, K.C.; Kataki, A.C.; Krishnatreya, M.; Jayalekshmi, P.A.; Sebastian, P.; Nandakumar, A.; Malekzadeh, R.; Roshandel, G.; Keinan-Boker, L.; Silverman, B.G.; Ito, H.; Nakagawa, H.; Sato, M.; Tobori, F.; Nakata, I.; Teramoto, N.; Hattori, M.; Kaizaki, Y.; Moki, F.; Sugiyama, H.; Utada, M.; Nishimura, M.; Yoshida, K.; Kurosawa, K.; Nemoto, Y.; Narimatsu, H.; Sakaguchi, M.; Kanemura, S.; Naito, M.; Narisawa, R.; Miyashiro, I.; Nakata, K.; Sato, S.; Yoshii, M.; Oki, I.; Fukushima, N.; Shibata, A.; Iwasa, K.; Ono, C.; Nimri, O.; Jung, K.W.; Won, Y.J.; Alawadhi, E.; Elbasmi, A.; Ab Manan, A.; Adam, F.; Sanjaajmats, E.; Tudev, U.; Ochir, C.; Al Khater, A.M.; El Mistiri, M.M.; Teo, Y.Y.; Chiang, C.J.; Lee, W.C.; Buasom, R.; Sangrajrang, S.; Kamsa-ard, S.; Wiangnon, S.; Daoprasert, K.; Pongnikorn, D.; Leklob, A.; Sangkitipaiboon, S.; Geater, S.L.; Sriplung, H.; Ceylan, O.; Kög, I.; Dirican, O.; Köse, T.; Gurbuz, T.; Karaşahin, F.E.; Turhan, D.; Aktaş, U.; Halat, Y.; Yakut, C.I.; Altinisik, M.; Cavusoglu, Y.; Türkköylü, A.; Üçüncü, N.; Hackl, M.; Zborovskaya, A.A.; Aleinikova, O.V.; Henau, K.; Van Eycken, L.; Valerianova, Z.; Yordanova, M.R.; Šekerija, M.; Dušek, L.; Zvolský, M.; Storm, H.; Innos, K.; Mägi, M.; Malila, N.; Seppä, K.; Jégu, J.; Velten, M.; Cornet, E.; Troussard, X.; Bouvier, A.M.; Guizard, A.V.; Bouvier, V.; Launoy, G.; Arveux, P.; Maynadié, M.; Mounier, M.; Woronoff, A.S.; Daoulas, M.; Robaszkiewicz, M.; Clavel, J.; Goujon, S.; Lacour, B.; Baldi, I.; Pouchieu, C.; Amadeo, B.; Coureau, G.; Orazio, S.; Preux, P.M.; Rharbaoui, F.; Marrer, E.; Trétarre, B.; Colonna, M.; Delafosse, P.; Ligier, K.; Plouvier, S.; Cowppli-Bony, A.; Molinié, F.; Bara, S.; Ganry, O.; Lapôtre-Ledoux, B.; Grosclaude, P.; Bossard, N.; Uhry, Z.; Bray, F.; Piñeros, M.; Stabenow, R.; Wilsdorf-Köhler, H.; Eberle, A.; Luttmann, S.; Löhden, I.; Nennecke, A.L.; Kieschke, J.; Sirri, E.; Emrich, K.; Zeissig, S.R.; Holleczek, B.; Eisemann, N.; Katalinic, A.; Asquez, R.A.; Kumar, V.; Petridou, E.; Ólafsdóttir, E.J.; Tryggvadóttir, L.; Clough-Gorr, K.; Walsh, P.M.; Sundseth, H.; Mazzoleni, G.; Vittadello, F.; Coviello, E.; Cuccaro, F.; Galasso, R.; Sampietro, G.; Giacomin, A.; Magoni, M.; Ardizzone, A.; D’Argenzio, A.; Castaing, M.; Grosso, G.; Lavecchia, A.M.; Sutera Sardo, A.; Gola, G.; Gatti, L.; Ricci, P.; Ferretti, S.; Serraino, D.; Zucchetto, A.; Celesia, M.V.; Filiberti, R.A.; Pannozzo, F.; Melcarne, A.; Quarta, F.; Russo, A.G.; Carrozzi, G.; Cirilli, C.; Cavalieri d’Oro, L.; Rognoni, M.; Fusco, M.; Vitale, M.F.; Usala, M.; Cusimano, R.; Mazzucco, W.; Michiara, M.; Sgargi, P.; Boschetti, L.; Borciani, E.; Seghini, P.; Maule, M.M.; Merletti, F.; Tumino, R.; Mancuso, P.; Vicentini, M.; Cassetti, T.; Sassatelli, R.; Falcini, F.; Giorgetti, S.; Caiazzo, A.L.; Cavallo, R.; Cesaraccio, R.; Pirino, D.R.; Contrino, M.L.; Tisano, F.; Fanetti, A.C.; Maspero, S.; Carone, S.; Mincuzzi, A.; Candela, G.; Scuderi, T.; Gentilini, M.A.; Piffer, S.; Rosso, S.; Barchielli, A.; Caldarella, A.; Bianconi, F.; Stracci, F.; Contiero, P.; Tagliabue, G.; Rugge, M.; Zorzi, M.; Beggiato, S.; Brustolin, A.; Berrino, F.; Gatta, G.; Sant, M.; Buzzoni, C.; Mangone, L.; Capocaccia, R.; De Angelis, R.; Zanetti, R.; Maurina, A.; Pildava, S.; Lipunova, N.; Vincerževskiené, I.; Agius, D.; Calleja, N.; Siesling, S.; Larønningen, S.; Møller, B.; Dyzmann-Sroka, A.; Trojanowski, M.; Góźdź, S.; Mężyk, R.; Mierzwa, T.; Molong, L.; Rachtan, J.; Szewczyk, S.; Błaszczyk, J.; Kępska, K.; Kościańska, B.; Tarocińska, K.; Zwierko, M.; Drosik, K.; Maksimowicz, K.M.; Purwin-Porowska, E.; Reca, E.; Wójcik-Tomaszewska, J.; Tukiendorf, A.; Grądalska-Lampart, M.; Radziszewska, A.U.; Gos, A.; Talerczyk, M.; Wyborska, M.; Didkowska, J.A.; Wojciechowska, U.; Bielska-Lasota, M.; Forjaz de Lacerda, G.; Rego, R.A.; Bastos, J.; Silva, M.A.; Antunes, L.; Laranja Pontes, J.; Mayer-da-Silva, A.; Miranda, A.; Blaga, L.M.; Coza, D.; Gusenkova, L.; Lazarevich, O.; Prudnikova, O.; Vjushkov, D.M.; Egorova, A.G.; Orlov, A.E.; Kudyakov, L.A.; Pikalova, L.V.; Adamcik, J.; Safaei Diba, C.; Primic-Žakelj, M.; Zadnik, V.; Larrañaga, N.; Lopez de Munain, A.; Herrera, A.A.; Redondas, R.; Marcos-Gragera, R.; Vilardell Gil, M.L.; Molina, E.; Sánchez Perez, M.J.; Franch Sureda, P.; Ramos Montserrat, M.; Chirlaque, M.D.; Navarro, C.; Ardanaz, E.E.; Guevara, M.M.; Fernández-Delgado, R.; Peris-Bonet, R.; Carulla, M.; Galceran, J.; Alberich, C.; Vicente-Raneda, M.; Khan, S.; Pettersson, D.; Dickman, P.; Avelina, I.; Staehelin, K.; Camey, B.; Bouchardy, C.; Schaffar, R.; Frick, H.; Herrmann, C.; Bulliard, J.L.; Maspoli-Conconi, M.; Kuehni, C.E.; Redmond, S.M.; Bordoni, A.; Ortelli, L.; Chiolero, A.; Konzelmann, I.; Matthes, K.L.; Rohrmann, S.; Broggio, J.; Rashbass, J.; Fitzpatrick, D.; Gavin, A.; Clark, D.I.; Deas, A.J.; Huws, D.W.; White, C.; Montel, L.; Rachet, B.; Turculet, A.D.; Stephens, R.; Chalker, E.; Phung, H.; Walton, R.; You, H.; Guthridge, S.; Johnson, F.; Gordon, P.; D’Onise, K.; Priest, K.; Stokes, B.C.; Venn, A.; Farrugia, H.; Thursfield, V.; Dowling, J.; Currow, D.; Hendrix, J.; Lewis, C. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): Analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125), 1023-1075.
[http://dx.doi.org/10.1016/S0140-6736(17)33326-3] [PMID: 29395269]
[5]
Monteiro, A.S.; Araújo, S.R.C.; Araujo, L.H.; Souza, M.C. Impact of microvascular invasion on 5-year overall survival of resected non-small cell lung cancer. J. Bras. Pneumol., 2022, 48(3), e20210283.
[http://dx.doi.org/10.36416/1806-3756/e20210283] [PMID: 35830051]
[6]
Pitale, P.M.; Howse, W.; Gorbatyuk, M. Neuronatin protein in health and disease. J. Cell. Physiol., 2017, 232(3), 477-481.
[http://dx.doi.org/10.1002/jcp.25498] [PMID: 27442611]
[7]
Xu, D.S.; Yang, C.; Proescholdt, M.; Bründl, E.; Brawanski, A.; Fang, X.; Lee, C.S.; Weil, R.J.; Zhuang, Z.; Lonser, R.R. Neuronatin in a subset of glioblastoma multiforme tumor progenitor cells is associated with increased cell proliferation and shorter patient survival. PLoS One, 2012, 7(5), e37811.
[http://dx.doi.org/10.1371/journal.pone.0037811] [PMID: 22624064]
[8]
Siu, I.M.; Bai, R.; Gallia, G.L.; Edwards, J.B.; Tyler, B.M.; Eberhart, C.G.; Riggins, G.J. Coexpression of neuronatin splice forms promotes medulloblastoma growth. Neuro-oncol., 2008, 10(5), 716-724.
[http://dx.doi.org/10.1215/15228517-2008-038] [PMID: 18701710]
[9]
Okubo, C.; Minami, Y.; Tanaka, R.; Uchihara, T.; Anami, Y.; Furuya, S.; Morishita, Y.; Iijima, T.; Noguchi, M. Analysis of differentially expressed genes in neuroendocrine carcinomas of the lung. J. Thorac. Oncol., 2006, 1(8), 780-786.
[http://dx.doi.org/10.1016/S1556-0864(15)30406-8] [PMID: 17409960]
[10]
Uchihara, T.; Okubo, C.; Tanaka, R.; Minami, Y.; Inadome, Y.; Iijima, T.; Morishita, Y.; Fujita, J.; Noguchi, M. Neuronatin expression and its clinicopathological significance in pulmonary non-small cell carcinoma. J. Thorac. Oncol., 2007, 2(9), 796-801.
[http://dx.doi.org/10.1097/JTO.0b013e318145af5e] [PMID: 17805055]
[11]
Cimino, I.; Rimmington, D.; Tung, Y.C.L.; Lawler, K.; Larraufie, P.; Kay, R.G.; Virtue, S.; Lam, B.Y.H.; Fagnocchi, L.; Ma, M.K.L.; Saudek, V.; Zvetkova, I.; Vidal-Puig, A.; Yeo, G.S.H.; Farooqi, I.S.; Pospisilik, J.A.; Gribble, F.M.; Reimann, F.; O’Rahilly, S.; Coll, A.P. Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity. Sci. Rep., 2021, 11(1), 17571.
[http://dx.doi.org/10.1038/s41598-021-96278-8] [PMID: 34475432]
[12]
Braun, J.L.; Teng, A.C.T.; Geromella, M.S.; Ryan, C.R.; Fenech, R.K.; MacPherson, R.E.K.; Gramolini, A.O.; Fajardo, V.A. Neuronatin promotes SERCA uncoupling and its expression is altered in skeletal muscles of high-fat diet-fed mice. FEBS Lett., 2021, 595(22), 2756-2767.
[http://dx.doi.org/10.1002/1873-3468.14213] [PMID: 34693525]
[13]
Braun, J.L.; Geromella, M.S.; Hamstra, S.I.; Fajardo, V.A. Neuronatin regulates whole-body metabolism: Is thermogenesis involved? FASEB Bioadv., 2020, 2(10), 579-586.
[http://dx.doi.org/10.1096/fba.2020-00052] [PMID: 33089074]
[14]
Schulz, R.; McCole, R.B.; Woodfine, K.; Wood, A.J.; Chahal, M.; Monk, D.; Moore, G.E.; Oakey, R.J. Transcript- and tissue-specific imprinting of a tumour suppressor gene. Hum. Mol. Genet., 2009, 18(1), 118-127.
[http://dx.doi.org/10.1093/hmg/ddn322] [PMID: 18836209]
[15]
Higashi, M.; Tajiri, T.; Kinoshita, Y.; Tatsuta, K.; Souzaki, R.; Maehara, Y.; Suita, S.; Taguchi, T. High expressions of neuronatin isoforms in favorable neuroblastoma. J. Pediatr. Hematol. Oncol., 2007, 29(8), 551-556.
[http://dx.doi.org/10.1097/MPH.0b013e3181256b7b] [PMID: 17762496]
[16]
Deng, Y.; Lu, L.; Liang, X.; Li, J.; Zhu, D.; Huang, H.; Zhang, Y.; Zhang, X.; Chen, Y.; Liu, X.; Fu, Y. DNA methylation-mediated silencing of Neuronatin promotes hepatocellular carcinoma proliferation through the PI3K-Akt signaling pathway. Life Sci., 2023, 312, 121266.
[http://dx.doi.org/10.1016/j.lfs.2022.121266] [PMID: 36473542]
[17]
Saeed, H.; Sinha, S.; Mella, C.; Kuerbitz, J.S.; Cales, M.L.; Steele, M.A.; Stanke, J.; Damron, D.; Safadi, F.; Kuerbitz, S.J. Aberrant epigenetic silencing of neuronatin is a frequent event in human osteosarcoma. Oncotarget, 2020, 11(20), 1876-1893.
[http://dx.doi.org/10.18632/oncotarget.27583] [PMID: 32499872]
[18]
Pieper, W.; Ignatov, A.; Kalinski, T.; Haybaeck, J.; Czapiewski, P.; Nass, N. The predictive potential of Neuronatin for neoadjuvant chemotherapy of breast cancer. Cancer Biomark., 2021, 32(2), 161-173.
[http://dx.doi.org/10.3233/CBM-203127] [PMID: 34092612]
[19]
Ryu, S.; McDonnell, K.; Choi, H.; Gao, D.; Hahn, M.; Joshi, N.; Park, S.M.; Catena, R.; Do, Y.; Brazin, J.; Vahdat, L.T.; Silver, R.B.; Mittal, V. Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration. Cancer Cell, 2013, 23(1), 63-76.
[http://dx.doi.org/10.1016/j.ccr.2012.11.019] [PMID: 23328481]
[20]
Yang, J.; Wei, J.; Wu, Y.; Wang, Z.; Guo, Y.; Lee, P.; Li, X. Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer. Oncogenesis, 2015, 4(6), e158.
[http://dx.doi.org/10.1038/oncsis.2015.18] [PMID: 26075749]
[21]
Rasmi, R.R.; Sakthivel, K.M.; Guruvayoorappan, C. NF-κB inhibitors in treatment and prevention of lung cancer. Biomed. Pharmacother., 2020, 130, 110569.
[http://dx.doi.org/10.1016/j.biopha.2020.110569] [PMID: 32750649]
[22]
Pastor, M.D.; Nogal, A.; Molina-Pinelo, S.; Meléndez, R.; Salinas, A.; González De la Peña, M.; Martín-Juan, J.; Corral, J.; García-Carbonero, R.; Carnero, A.; Paz-Ares, L. Identification of proteomic signatures associated with lung cancer and COPD. J. Proteomics, 2013, 89, 227-237.
[http://dx.doi.org/10.1016/j.jprot.2013.04.037] [PMID: 23665002]
[23]
Guttridge, D.C.; Albanese, C.; Reuther, J.Y.; Pestell, R.G.; Baldwin, A.S., Jr NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell. Biol., 1999, 19(8), 5785-5799.
[http://dx.doi.org/10.1128/MCB.19.8.5785] [PMID: 10409765]
[24]
Gyrd-Hansen, M.; Meier, P. IAPs: From caspase inhibitors to modulators of NF-κB, inflammation and cancer. Nat. Rev. Cancer, 2010, 10(8), 561-574.
[http://dx.doi.org/10.1038/nrc2889] [PMID: 20651737]
[25]
Zhao, H.; Wu, L.; Yan, G.; Chen, Y.; Zhou, M.; Wu, Y.; Li, Y. Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct. Target. Ther., 2021, 6(1), 263.
[http://dx.doi.org/10.1038/s41392-021-00658-5] [PMID: 34248142]
[26]
Yang, C.J.; Liu, Y.P.; Dai, H.Y.; Shiue, Y.L.; Tsai, C.J.; Huang, M.S.; Yeh, Y.T. Nuclear HDAC6 inhibits invasion by suppressing NF-κB/MMP2 and is inversely correlated with metastasis of non-small cell lung cancer. Oncotarget, 2015, 6(30), 30263-30276.
[http://dx.doi.org/10.18632/oncotarget.4749] [PMID: 26388610]
[27]
Mzhavia, N.; Yu, S.; Ikeda, S.; Chu, T.T.; Goldberg, I.; Dansky, H.M. Neuronatin: A new inflammation gene expressed on the aortic endothelium of diabetic mice. Diabetes, 2008, 57(10), 2774-2783.
[http://dx.doi.org/10.2337/db07-1746] [PMID: 18591389]
[28]
Gysler, S.M.; Drapkin, R. Tumor innervation: Peripheral nerves take control of the tumor microenvironment. J. Clin. Invest., 2021, 131(11), e147276.
[http://dx.doi.org/10.1172/JCI147276] [PMID: 34060481]
[29]
Saloman, J.L.; Albers, K.M.; Rhim, A.D.; Davis, B.M. Can stopping nerves, stop cancer? Trends Neurosci., 2016, 39(12), 880-889.
[http://dx.doi.org/10.1016/j.tins.2016.10.002] [PMID: 27832915]
[30]
Cervantes-Villagrana, R.D.; Albores-García, D.; Cervantes-Villagrana, A.R.; García-Acevez, S.J. Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies. Signal Transduct. Target. Ther., 2020, 5(1), 99.
[http://dx.doi.org/10.1038/s41392-020-0205-z] [PMID: 32555170]
[31]
Talmadge, J.E.; Fidler, I.J. AACR centennial series: The biology of cancer metastasis: historical perspective. Cancer Res., 2010, 70(14), 5649-5669.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1040] [PMID: 20610625]
[32]
Joseph, R.M. Neuronatin gene: Imprinted and misfolded. Genomics, 2014, 103(2-3), 183-188.
[http://dx.doi.org/10.1016/j.ygeno.2013.12.001] [PMID: 24345642]
[33]
Li, B.; Xu, H.; He, C.; Zou, W.; Tu, Y. Lidocaine prevents breast cancer growth by targeting neuronatin to inhibit nerve fibers formation. J. Toxicol. Sci., 2021, 46(7), 329-339.
[http://dx.doi.org/10.2131/jts.46.329] [PMID: 34193770]

© 2024 Bentham Science Publishers | Privacy Policy