[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.14348/molcells.2014.2353

NF-κB in Cellular Senescence and Cancer Treatment

Jing, Hua (MKFZ, Charite - Universitatsmedizin Berlin and Max-Delbruck-Centrum for Molecular Medicine)
Lee, Soyoung (MKFZ, Charite - Universitatsmedizin Berlin and Max-Delbruck-Centrum for Molecular Medicine)

Abstract

The NF- ${\kappa}B$ pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses. While many studies showed anti-tumorigenic and pro-survival role of NF- ${\kappa}B$ in cancer cells, recent findings postulate that NF- ${\kappa}B$ participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF- ${\kappa}B$ . In this review, we discuss implications of the NF- ${\kappa}B$ signaling pathway in cancer. Particularly, we emphasize the connection of NF- ${\kappa}B$ with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF- ${\kappa}B$ produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.

Keywords

cancer; chemotherapy; NF- ${\kappa}B$ ; senescence;

Citations & Related Records

Reference

1	Davis, R.E., Brown, K.D., Siebenlist, U., and Staudt, L.M. (2001). Constitutive nuclear factor kappa B activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J. Exp. Med. 194, 1861-1874. DOI
2	Huang, J.Z., Sanger, W.G., Greiner, T.C., Staudt, L.M., Weisenburger, D.D., Pickering, D.L., Lynch, J.C., Armitage, J.O., Warnke, R.A., Alizadeh, A.A., et al. (2002). The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 99, 2285-2290. DOI ScienceOn
3	Inokuchi, S., Aoyama, T., Miura, K., Osterreicher, C.H., Kodama, Y., Miyai, K., Akira, S., Brenner, D.A., and Seki, E. (2010). Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis. Proc. Natl. Acad. Sci. USA 107, 844-849. DOI ScienceOn
4	Iqbal, J., Sanger, W.G., Horsman, D.E., Rosenwald, A., Pickering, D.L., Dave, B., Dave, S., Xiao, L., Cao, K., Zhu, Q., et al. (2004). BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. Am. J. Pathol. 165, 159-166. DOI ScienceOn
5	Kaltschmidt, B., Kaltschmidt, C., Hofmann, T.G., Hehner, S.P., Droge, W., and Schmitz, M.L. (2000). The pro- or anti-apoptotic function of NF-kappaB is determined by the nature of the apoptotic stimulus. Eur. J. Biochem. 267, 3828-3835. DOI ScienceOn
6	Coppe, J.P., Patil, C.K., Rodier, F., Sun, Y., Munoz, D.P., Goldstein, J., Nelson, P.S., Desprez, P.Y., and Campisi, J. (2008). Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853-2868.
7	Coppe, J.P., Desprez, P.Y., Krtolica, A., and Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99-118. DOI ScienceOn
8	Franzoso, G., Bours, V., Park, S., Tomita-Yamaguchi, M., Kelly, K., and Siebenlist, U. (1992). The candidate oncoprotein Bcl-3 is an antagonist of p50/NF- $\kappa{B}$ -mediated inhibition. Nature 359, 339-342. DOI ScienceOn
9	Guttridge, D.C., Albanese, C., Reuther, J.Y., Pestell, R.G., and Baldwin, A.S. Jr. (1999). NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell. Biol. 19, 5785-5799. DOI
10	Grivennikov, S., Greten, F.R., and Karin, M. (2010). Immunity, inflammation, and cancer. Cell 140, 883-899. DOI ScienceOn
11	Hayden, M.S., and Ghosh, S. (2004). Signaling to NF-kappaB. Genes Dev. 18, 2195-2224. DOI ScienceOn
12	Hayden, M.S., and Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell 132, 344-362. DOI ScienceOn
13	Heyninck, K., and Beyaert, R. (2005). A20 inhibits NF- $\kappa{B}$ activation by dual ubiquitin-editing functions. Trends Biochem. Sci. 30, 1-4. DOI ScienceOn
14	Lim, K.H., Yang, Y., and Staudt, L.M. (2012). Pathogenetic importance and therapeutic implications of NF- $\kappa{B}$ in lymphoid malignancies. Immunol. Rev. 246, 359-378. DOI ScienceOn
15	Lam, L.T., Davis, R.E., Pierce, J., Hepperle, M., Xu, Y., Hottelet, M., Nong, Y., Wen, D., Adams, J., Dang, L., et al. (2005). Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling. Clin. Cancer Res. 11, 28-40.
16	Lenz, G., Davis, R.E., Ngo, V.N., Lam, L., George, T.C., Wright, G. W., Dave, S.S., Zhao, H., Xu, W., Rosenwald, A., et al. (2008a). Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319, 1676-1679. DOI ScienceOn
17	Lenz, G., Wright, G., Dave, S.S., Xiao, W., Powell, J., Zhao, H., Xu, W., Tan, B., Goldschmidt, N., Iqbal, J., et al. (2008b). Stromal gene signatures in large-B-cell lymphomas. N. Engl. J. Med. 359, 2313-232. DOI ScienceOn
18	Luedde, T., Beraza, N., Kotsikoris, V., van Loo, G., Nenci, A., De Vos, R., Roskams, T., Trautwein, C., and Pasparakis, M. (2007). Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 11, 119-132. DOI ScienceOn
19	Martin, A.G., Trama, J., Crighton, D., Ryan, K.M., and Fearnhead, H.O. (2009). Activation of p73 and induction of Noxa by DNA damage requires NF-kappa B. Aging 1, 335-349. DOI
20	Maeda, S., Kamata, H., Luo, J.L., Leffert, H., and Karin, M. (2005). IKK couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121, 977-990. DOI ScienceOn
21	Compagno, M., Lim, W.K., Grunn, A., Nandula, S.V., Brahmachary, M., Shen, Q., Bertoni, F., Ponzoni, M., Scandurra, M., Califano, A., et al. (2009). Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 459, 717-721. DOI ScienceOn
22	Keats, J.J., Fonseca, R., Chesi, M., Schop, R., Baker, A., Chng, W.J., Van Wier, S., Tiedemann, R., Shi, C.X., Sebag, M., et al. (2007). Promiscuous mutations activate the noncanonical NF- $\kappa{B}$ pathway in multiple myeloma. Cancer Cell 12, 131-144. DOI ScienceOn
23	Schneider, A., Martin-Villalba, A., Weih, F., Vogel, J., Wirth, T., and Schwaninger, M. (1999). NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat. Med. 5, 554-559. DOI ScienceOn
24	Seitz, C.S., Lin, Q., Deng, H., and Khavari, P.A. (1998). Alterations in NF- $\kappa{B}$ function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF- $\kappa{B}$ . Proc. Natl. Acad. Sci. USA 95, 2307-2312. DOI
25	Keller, U., Huber, J., Nilsson, J.A., Fallahi, M., Hall, M.A., Peschel, C., and Cleveland, J.L. (2010). Myc suppression of Nfkb2 accelerates lymphomagenesis. BMC Cancer 10, 348. DOI ScienceOn
26	Kortlever, R.M., Higgins, P.J., and Bernards, R. (2006). Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat. Cell Biol. 8, 877-884. DOI
27	Rosenwald, A., Wright, G., Chan, W.C., Connors, J.M., Campo, E., Fisher, R.I., Gascoyne, R.D., Muller-Hermelink, H.K., Smeland, E.B., Giltnane, J.M., et al. (2002). The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 346, 1937-1947. DOI ScienceOn
28	Kuilman, T., and Peeper, D.S. (2009). Senescence-messaging secretome: SMS-ing cellular stress. Nat. Rev. Cancer 9, 81-94. DOI ScienceOn
29	Kuilman, T., Michaloglou, C., Vredeveld, L.C., Douma, S., van Doorn, R., Desmet, C.J., Aarden, L.A., Mooi, W.J., and Peeper, D.S. (2008). Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019-1031. DOI ScienceOn
30	Kuilman, T., Michaloglou, C., Mooi, W.J., and Peeper, D.S. (2010). The essence of senescence. Genes Dev. 24, 2463-2479. DOI ScienceOn
31	Prasad, S., Ravindran, J., and Aggarwal, B.B. (2010). NF-kappaB and cancer: how intimate is this relationship. Mol. Cell. Biochem. 336, 25-37. DOI
32	Reimann, M., Lee, S., Loddenkemper, C., Dorr, J.R., Tabor, V., Aichele, P., Stein, H., Dorken, B., Jenuwein, T., and Schmitt, C. A. (2010). Tumor stroma-derived TGF-beta limits myc-driven lymphomagenesis via Suv39h1-dependent senescence. Cancer Cell. 17, 262-272. DOI ScienceOn
33	Rovillain, E., Mansfield, L., Caetano, C., Alvarez-Fernandez, M., Caballero, O.L., Medema, R.H., Hummerich, H., and Jat, P.S. (2011). Activation of nuclear factor-kappa B signalling promotes cellular senescence. Oncogene 30, 2356-2366. DOI ScienceOn
34	Ryan, K.M., Ernst, M.K., Rice, N.R., and Vousden, K.H. (2000). Role of NF-kappaB in p53-mediated programmed cell death. Nature 404, 892-897. DOI ScienceOn
35	Schmitt, C.A. (2007). Cellular senescence and cancer treatment. Biochim. Biophys. Acta 1775, 5-20.
36	Yang, J., Splittgerber, R., Yull, F.E., Kantrow, S., Ayers, G.D., Karin, M., and Richmond, A. (2010). Conditional ablation of Ikk $\beta$ inhibits melanoma tumor development in mice. J. Clin. Invest. 120, 2563-2574. DOI ScienceOn
37	Schmitt, C.A., Fridman, J.S., Yang, M., Lee, S., Baranov, E., Hoffman, R.M., and Lowe, S.W. (2002). A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109, 335-346. DOI ScienceOn
38	Sheehy, A.M., and Schlissel, M.S. (1999). Overexpression of RelA causes G1 arrest and apoptosis in a Pro-B cell line. J. Biol. Chem. 274, 8708-8716. DOI ScienceOn
39	Yamamoto, K., Arakawa, T., Ueda, N., and Yamamoto, S. (1995). Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. J. Biol. Chem. 270, 31315-31320. DOI
40	Sen, R., and Baltimore, D. (1986). Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46, 705-716. DOI ScienceOn
41	Neri, A., Chang, C.C., Lombardi, L., Salina, M., Corradini, P., Maiolo, AT., Chaganti, R.S., and Dalla-Favera, R. (1991). B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF- $\kappa{B}$ p50. Cell 67, 1075-1087. DOI ScienceOn
42	Ngo, V.N., Young, R.M., Schmitz, R., Jhavar, S., Xiao, W., Lim, K.H., Kohlhammer, H., Xu, W., Yang, Y., Zhao, H., et al. (2011). Oncogenically active MYD88 mutations in human lymphoma. Nature 470, 115-119. DOI ScienceOn
43	Perkins, N.D. (2007). Integrating cell-signalling pathways with NFkappaB and IKK function. Nat. Rev. Mol. Cell Biol. 8, 49-62. DOI ScienceOn
44	te Poele, R.H., Okorokov, A.L., Jardine, L., Cummings, J., and Joel, S.P. (2002). DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res. 62, 1876-1883.
45	Wang, C.Y., Mayo, M.W., Korneluk, R.G., Goeddel, D.V., and Baldwin, A.S. Jr. (1998). NF- $\kappa{B}$ antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281, 1680-1683. DOI ScienceOn
46	Sun, L., Deng, L., Ea, C.K., Xia, Z.P., and Chen, Z.J. (2004). The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol. Cell 14, 289-301. DOI ScienceOn
47	Tamatani, M., Che, Y.H., Matsuzaki, H., Ogawa, S., Okado, H., Miyake, S., Mizuno, T., and Tohyama, M. (1999). Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons. J. Biol. Chem. 274, 8531-8538. DOI ScienceOn
48	Tu, S., Bhagat, G., Cui, G., Takaishi, S., Kurt-Jones, E.A., Rickman, B., Betz, K.S., Penz-Oesterreicher, M., Bjorkdahl, O., Fox, J.G., et al. (2008). Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14, 408-419. DOI ScienceOn
49	Wertz, I.E., O'Rourke, K.M., Zhou, H., Eby, M., Aravind, L., Seshagiri, S., Wu, P., Wiesmann, C., Baker, R., Boone, D.L., et al. (2004). De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF- $\kappa{B}$ signalling. Nature 430, 694-699. DOI ScienceOn
50	Xue, W., Zender, L., Miething, C., Dickins, R.A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., and Lowe, S.W. (2007). Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656-660. DOI ScienceOn
51	Chang, B.D., Broude, E.V., Dokmanovic, M., Zhu, H., Ruth, A., Xuan, Y., Kandel, ES., Lausch, E., Christov, K., and Roninson, I.B. (1999). A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Res. 59, 3761-3767.
52	Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A.H., Schlegelberger, B., Stein, H., Dorken, B., Jenuwein, T., and Schmitt, C.A. (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436, 660-665. DOI ScienceOn
53	Calado, D.P., Zhang, B., Srinivasan, L., Sasaki, Y., Seagal, J., Unitt, C., Rodig, S., Kutok, J., Tarakhovsky, A., Schmidt-Supprian, M., et al. (2010). Constitutive canonical NF- $\kappa{B}$ activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma. Cancer Cell 18, 580-589. DOI ScienceOn
54	Catz, S.D., and Johnson, J.L. (2001). Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 20, 7342-7351. DOI ScienceOn
55	Zhou, H., Wertz, I., O'Rourke, K., Ultsch, M., Seshagiri, S., Eby, M., Xiao, W., and Dixit, V.M. (2004). Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature 427, 167-171. DOI ScienceOn
56	Staudt, L.M. (2010). Oncogenic activation of NF- $\kappa{B}$ . Cold Spring Harb Perspect Biol. 2, a000109.
57	Acosta, J.C., O'Loghlen, A., Banito, A., Guijarro, M.V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008). Chemokine Signaling via the CXCR2 Receptor Reinforces Senescence. Cell 133, 1006-1018. DOI ScienceOn
58	Stehlik, C., de Martin. R., Kumabashiri, I., Schmid, J.A., Binder, B.R., and Lipp, J. (1998). Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J. Exp. Med. 188, 211-216. DOI ScienceOn
59	Arkan, M.C., and Greten, F.R. (2011). IKK- and NF- $\kappa{B}$ -mediated functions in carcinogenesis. Curr. Top. Microbiol. Immunol. 349, 159-169.
60	Annunziata, C.M., Davis, R.E., Demchenko, Y., Bellamy, W., Gabrea, A., Zhan, F., Lenz, G., Hanamura, I., Wright, G., Xiao, W., et al. (2007). Frequent engagement of the classical and alternative NF- $\kappa{B}$ pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell 12, 115-130. DOI ScienceOn
61	Alizadeh, A.A., Eisen, M.B., Davis, R.E., Ma, C., Lossos, I.S., Rosenwald, A., Boldrick, J.C., Sabet, H., Tran, T., Yu, X., et al. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403, 503-511. DOI ScienceOn
62	Baldwin, A.S. (2001). Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J. Clin. Invest. 107, 241-246. DOI ScienceOn
63	Basseres, D.S., and Baldwin, A.S. (2006). Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene 25, 6817-6830. DOI ScienceOn
64	Basseres, D.S., Ebbs, A., Levantini, E., and Baldwin, A.S. (2010). Requirement of the NF- $\kappa{B}$ subunit p65/RelA for K-Ras-induced lung tumorigenesis. Cancer Res. 70, 3537-354. DOI
65	Zhu, L., Fukuda, S., Cordis, G., Das, D.K., and Maulik, N. (2001). Anti-apoptotic protein surviving plays a significant role in tubular morphogenesis of human coronary arteriolar endothelial cells by hypoxic preconditioning. FEBS Lett. 508, 369-374. DOI ScienceOn
66	Ben-Neriah, Y., and Karin, M. (2011). Inflammation meets cancer, with NF- $\kappa{B}$ as the matchmaker. Nat. Immunol. 12, 715-723. DOI ScienceOn
67	Bonizzi, G., and Karin, M. (2004). The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 25, 280-288. DOI ScienceOn
68	Kasibhatla, S., Genestier, L., and Green, D.R. (1999). Regulation of fas-ligand expression during activation-induced cell death in T lymphocytes via nuclear factor kappaB. J. Biol. Chem. 274, 987-992. DOI ScienceOn
69	Popivanova, B.K., Kitamura, K., Wu, Y., Kondo, T., Kagaya, T., Kaneko, S., Oshima, M., Fujii, C., and Mukaida, N. (2008). Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J. Clin. Invest. 118, 560-570.
70	Ngo, V.N., Davis, R.E., Lamy, L., Yu, X., Zhao, H., Lenz, G., Lam, L.T., Dave, S., Yang, L., Powell, J., et al. (2006). A loss-offunction RNA interference screen for molecular targets in cancer. Nature 441, 106-110. DOI ScienceOn

Reference

1	Lea-Yea Chuang. (2016) Toxicol. Res. Effects of probucol on cell proliferation in human ovarian cancer cells / 5 (1) , 331
6	Nahla E. El-Ashmawy. (2016) Nutrition and Cancer Effect of Pomegranate Hull Extract on Liver Neoplastic Changes in Rats: More than an Antioxidant / 68 (6) , 1044
	Jie Jin. (2016) Biomedicine & Pharmacotherapy TMPRSS4 promotes invasiveness of human gastric cancer cells through activation of NF-κB/MMP-9 signaling / 77 , 30
1	EDUARDO FUENTES. (2017) Anais da Academia Brasileira de Ciências Immune System Dysfunction in the Elderly / 89 (1) , 285
8	Anne G. Christensen. (2017) STEM CELLS Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening / 35 (8) , 1898
5	Shu Li. (2015) Oncology Reports Farnesoid X receptor signal is involved in deoxycholic acid-induced intestinal metaplasia of normal human gastric epithelial cells / 34 (5) , 2674
	Jun-Yi Luo. (2017) Journal of Molecular and Cellular Cardiology Mutant DD genotype of NFKB1 gene is associated with the susceptibility and severity of coronary artery disease / 103 , 56
2	Yu Sun. (2015) Medicinal Research Reviews Translational Horizons in the Tumor Microenvironment: Harnessing Breakthroughs and Targeting Cures / 35 (2) , n/a
3	Qingying Luo. (2015) The Journal of Toxicological Sciences The role of NF-κB in PARP-inhibitor-mediated sensitization and detoxification of arsenic trioxide in hepatocellular carcinoma cells / 40 (3) , 349
6	Chie Ishikawa. (2015) International Journal of Oncology Induction of IκB-ζ by Epstein-Barr virus latent membrane protein-1 and CD30 / 47 (6) , 2197
6	Mengqiu Wu. (2017) Journal of Proteome Research Metabolomics–Proteomics Combined Approach Identifies Differential Metabolism-Associated Molecular Events between Senescence and Apoptosis / 16 (6) , 2250
4	Chieh-Tien Shih. (2017) Aging Cell The PPARγ-SETD8 axis constitutes an epigenetic, p53-independent checkpoint on p21-mediated cellular senescence / 16 (4) , 797
4	Manuel Scimeca. (2016) Tumor Biology Emerging prognostic markers related to mesenchymal characteristics of poorly differentiated breast cancers / 37 (4) , 5427
4	K. A. Szcześniak. (2016) Journal of Animal Physiology and Animal Nutrition Investigation of nutriactive phytochemical - gamma-oryzanol in experimental animal models / 100 (4) , 601
	Shu-Zhi Wang. (2015) Evidence-Based Complementary and Alternative Medicine Cobrotoxin fromNaja naja atraVenom Ameliorates Adriamycin Nephropathy in Rats / 2015 , 1
2	Nahla E. El-Ashmawy. (2017) Clinical and Experimental Medicine Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor / 17 (2) , 185
1	Hui Peng. (2017) Military Medical Research PM2.5 obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B / 4 (1)
10	Khosrow Rezvani. (2016) International Journal of Molecular Sciences UBXD Proteins: A Family of Proteins with Diverse Functions in Cancer / 17 (10) , 1724
1	(2018) Biological Procedures Online Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence / 20 (1)
6	(2016) Oncology Letters Upregulation of microRNA-181b inhibits CCL18-induced breast cancer cell metastasis and invasion via the NF-κB signaling pathway / 12 (6) , 4411
4	(2018) Experimental and therapeutic medicine Protective effect and molecular mechanism of liquiritin on oxybuprocaine-induced apoptosis of human corneal endothelial cells / 15 (4) , 3432
11	(2018) Cancers NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses—Therapeutic Perspectives / 10 (11) , 426
11	(2018) Journal of Virology Exacerbated Apoptosis of Cells Infected with Infectious Bursal Disease Virus upon Exposure to Interferon Alpha / 92 (11)
5	(2018) Nature Reviews Immunology NF-κB, inflammation, immunity and cancer: coming of age / 18 (5) , 309
2	(2019) Cells Essential Roles for the Non-Canonical IκB Kinases in Linking Inflammation to Cancer, Obesity, and Diabetes / 8 (2) , 178
40	(2016) Oncotarget The BCR-ABL/NF-κB signal transduction network: a long lasting relationship in Philadelphia positive Leukemias / 7 (40) , 66287
7	(2016) Cancer prevention research Diallyl Disulfide (DADS), a Constituent of Garlic, Inactivates NF-κB and Prevents Colitis-Induced Colorectal Cancer by Inhibiting GSK-3β / 9 (7) , 607
11	(2014) Aging Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation / 8 (11) , 3065
6	(2014) Current genomics Regulation of Age-related Decline by Transcription Factors and Their Crosstalk with the Epigenome / 19 (6) , 464
5	(2014) Oncology reports KLF5 promotes the tumorigenesis and metastatic potential of thyroid cancer cells through the NF-κB signaling pathway / 40 (5) , 2608
None	(2019) Scientific reports Senescence-related deterioration of intercellular junctions in the peritoneal mesothelium promotes the transmesothelial invasion of ovarian cancer cells / 9 (None) , 7587
4	(2014) International journal of molecular medicine MicroRNA-199a-5p functions as a tumor suppressor in oral squamous cell carcinoma via targeting the IKKβ/NF-κB signaling pathway / 43 (4) , 1585
17	(2014) Aging lncRNA <I>miat</I> functions as a ceRNA to upregulate <I>sirt1</I> by sponging <I>miR-22-3p</I> in HCC cellular senescence / 11 (17) , 7098
None	(2020) Current stem cell research & therapy Stem Cell Aging in Lifespan and Disease: A State-of-the-Art Review / 15 (None) , 362
None	(2020) Frontiers in pharmacology Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling / 11 (None) , 572616
9	(2014) International journal of molecular sciences Cellular Senescence in the Lung: The Central Role of Senescent Epithelial Cells / 21 (9) , 3279
1	(2020) Scientific reports <I>NFKB1</I> gene rs28362491 ins/del variation is associated with higher susceptibility to myocardial infarction in a Chinese Han population / 10 (1) , 19518
None	(2014) Cancer treatment and research communications The emerging role of cellular senescence in complications of COVID-19 / 28 (None) , 100399
None	(2014) Frontiers in neuroscience The Repression of the HMGB1-TLR4-NF-κB Signaling Pathway by Safflower Yellow May Improve Spinal Cord Injury / 15 (None) , 803885
8	(2014) Biomedicines NF-κB and Human Cancer: What Have We Learned over the Past 35 Years? / 9 (8) , 889
1	(2014) Experimental and therapeutic medicine LIM mineralization protein‑1 inhibits IL‑1β‑induced human chondrocytes injury by altering the NF‑κB and MAPK/JNK pathways / 23 (1) , 61
4	(2014) Medcomm NF‐κB signaling in inflammation and cancer / 2 (4) , 618