Cancer secretome and inflammation: The bright and the dark sides of NF-κB

Seminars in Cell and Developmental Biology

Volumn 78, Issue , 2018, Pages 51-61

  Capece, Daria ^a,b   Verzella, Daniela ^a,b   Tessitore, Alessandra ^a   Alesse, Edoardo ^a   Capalbo, Carlo ^c   Zazzeroni, Francesca ^a  

^a UNIVERSITY OF L'AQUILA   (Italy)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Immunity; Inflammation; NF B; SASP; Secretome; Senescence

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; I KAPPA B; PROTEOME; RELA PROTEIN, HUMAN; TRANSCRIPTION FACTOR RELA;

ADAPTIVE IMMUNITY; CELL PROLIFERATION; CHRONIC INFLAMMATION; ENZYME ACTIVATION; GENETIC TRANSCRIPTION; HUMAN; INFLAMMATION; MACROPHAGE; MALIGNANT NEOPLASM; REGULATORY MECHANISM; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT; TUMOR RECURRENCE; CELL TRANSFORMATION; IMMUNOLOGY; INNATE IMMUNITY; METABOLISM; NEOPLASM; PATHOLOGY;

CELL TRANSFORMATION, NEOPLASTIC; HUMANS; I-KAPPA B PROTEINS; IMMUNITY, INNATE; INFLAMMATION; NEOPLASMS; PROTEOME; TRANSCRIPTION FACTOR RELA; TUMOR MICROENVIRONMENT;

EID: 85028601420     PISSN: 10849521     EISSN: 10963634     Source Type: Journal    
DOI: 10.1016/j.semcdb.2017.08.004     Document Type: Review

References (124)

1. Tjalsma, H., Bolhuis, A., Jongbloed, J.D., Bron, S., van Dijl, J.M., Signal peptide-dependent protein transport in Bacillus subtilis: a genome-based survey of the secretome. Microbiol. Mol. Biol. Rev. 64:3 (2000), 515–547.
2. Agrawal, G.K., Jwa, N.S., Lebrun, M.H., Job, D., Rakwal, R., Plant secretome: unlocking secrets of the secreted proteins. Proteomics 10:4 (2010), 799–827.
3. Zullo, J., Matsumoto, K., Xavier, S., Ratliff, B., Goligorsky, M.S., The cell secretome, a mediator of cell-to-cell communication. Prostaglandins Other Lipid Mediat. 120 (2015), 17–20.
4. Kastelowitz, N., Yin, H., Exosomes and microvesicles: identification and targeting by particle size and lipid chemical probes. Chembiochem 15:7 (2014), 923–928.
5. Mukherjee, P., Mani, S., Methodologies to decipher the cell secretome. Biochim. Biophys. Acta 1834:11 (2013), 2226–2232.
6. Dolberg, D.S., Bissell, M.J., Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309:5968 (1984), 552–556.
7. Grivennikov, S.I., Greten, F.R., Karin, M., Immunity, inflammation, and cancer. Cell 140:6 (2010), 883–899, 10.1016/j.cell.2010.01.025.
8. Colotta, F., Allavena, P., Sica, A., Garlanda, C., Mantovani, A., Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30:7 (2009), 1073–1081.
9. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144:5 (2011), 646–674.
10. Qian, B.Z., Pollard, J.W., Macrophage diversity enhances tumor progression and metastasis. Cell 141:1 (2010), 39–51.
11. Freund, A., Orjalo, A.V., Desprez, P.Y., Campisi, J., Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med. 16:5 (2010), 238–246.
12. Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., Kirkland, J.L., Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest. 123:3 (2013), 966–972.
13. Acosta, J.C., O'Loghlen, A., Banito, A., Guijarro, M.V., Augert, A., Raguz, S., et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133:6 (2008), 1006–1018.
14. Kuilman, T., Michaloglou, C., Vredeveld, L.C., Douma, S., van Doorn, R., Desmet, C.J., et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133:6 (2008), 1019–1031.
15. Coppé, J.P., Patil, C.K., Rodier, F., Sun, Y., Muñoz, D.P., Goldstein, J., et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6:12 (2008), 2853–2868.
16. Rodier, F., Coppé, J.P., Patil, C.K., Hoeijmakers, W.A., Muñoz, D.P., Raza, S.R., et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11:8 (2009), 973–979.
17. Karin, M., Cao, Y., Greten, F.R., Li, Z.W., NF-kappaB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer 2:4 (2002), 301–310.
18. Ben-Neriah, Y., Karin, M., Inflammation meets cancer, with NF-κB as the matchmaker. Nat. Immunol. 12:8 (2011), 715–723.
19. DiDonato, J.A., Mercurio, F., Karin, M., NF-κB and the link between inflammation and cancer. Immunol. Rev. 246:1 (2012), 379–400.
20. Sen, R., Baltimore, D., Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46:5 (1986), 705–716.
21. Hayden, M.S., Ghosh, S., NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 26:3 (2012), 203–234.
22. Oeckinghaus, A., Ghosh, S., The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol., 1(4), 2009, a000034.
23. Hoesel, B., Schmid, J.A., The complexity of NF-κB signaling in inflammation and cancer. Mol. Cancer, 12, 2013, 86.
24. Perkins, N.D., The diverse and complex roles of NF-κB subunits in cancer. Nat. Rev. Cancer 12:January (2) (2012), 121–132.
25. Baud, V., Is, Karin M., NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat. Rev. Drug Discov. 8:1 (2009), 33–40.
26. Xia, Y., Shen, S., Verma, I.M., NF-κB an active player in human cancers. Cancer Immunol Res. 2:9 (2014), 823–830.
27. Bassères, D.S., Baldwin, A.S., Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene 25:51 (2006), 6817–6830.
28. Prasad, S., Ravindran, J., Aggarwal, B.B., NF-kappaB and cancer: how intimate is this relationship. Mol. Cell. Biochem. 336:1-2 (2010), 25–37.
29. Cooks, T., Pateras, I.S., Tarcic, O., Solomon, H., Schetter, A.J., Wilder, S., et al. Mutant p53 prolongs NF-κB activation and promotes chronic inflammation and inflammation-associated colorectal cancer. Cancer Cell 23:5 (2013), 634–646.
30. Di Minin, G., Bellazzo, A., Dal Ferro, M., Chiaruttini, G., Nuzzo, S., Bicciato, S., et al. Mutant p53 reprograms TNF signaling in cancer cells through interaction with the tumor suppressor DAB2IP. Mol. Cell 56:5 (2014), 617–629.
31. Boldin, M.P., Baltimore, D., MicroRNAs, new effectors and regulators of NF-κB. Immunol. Rev. 246:1 (2012), 205–220.
32. Polytarchou, C., Hommes, D.W., Palumbo, T., Hatziapostolou, M., Koutsioumpa, M., Koukos, G., et al. MicroRNA214 is associated with progression of ulcerative colitis, and inhibition reduces development of colitis and colitis-Associated cancer in mice. Gastroenterology 149:4 (2015), 981–992.
33. Mao, X., Su, Z., Mookhtiar, A.K., Long non-coding RNA: a versatile regulator of the nuclear factor-κB signalling circuit. Immunology 150:4 (2017), 379–388.
34. Tornatore, L., Thotakura, A.K., Bennett, J., Moretti, M., Franzoso, G., The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation. Trends Cell Biol. 22:11 (2012), 557–566.
35. Johnson, R.F., Perkins, N.D., Nuclear factor-κB, p53, and mitochondria: regulation of cellular metabolism and the Warburg effect. Trends Biochem. Sci. 37:8 (2012), 317–324.
36. Elinav, E., Nowarski, R., Thaiss, C.A., Hu, B., Jin, C., Flavell, R.A., Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat. Rev. Cancer 13:11 (2013 Nov), 759–771.
37. Quail, D.F., Joyce, J.A., Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19 (2013), 1423–1437.
38. Terzic, J., Grivennikov, S., Karin, E., Karin, M., Inflammation and colon cancer. Gastroenterology 138 (2010), 2101–2114.
39. Mantovani, A., Allavena, P., Sica, A., Balkwill, F., Cancer-related inflammation. Nature 454 (2008), 436–444.
40. Sparmann, A., Bar-Sagi, D., Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6:5 (2004), 447–458.
41. Schauer, I.G., Zhang, J., Xing, Z., Guo, X., Mercado-Uribe, I., Sood, A.K., et al. Interleukin-1β promotes ovarian tumorigenesis through a p53/NF-κB-mediated inflammatory response in stromal fibroblasts. Neoplasia 15:4 (2013), 409–420.
42. Li, X., Wang, S., Zhu, R., Li, H., Han, Q., Zhao, R.C., Lung tumor exosomes induce a pro-inflammatory phenotype in mesenchymal stem cells via NFκB-TLR signaling pathway. J Hematol Oncol., 9, 2016, 42.
43. Iliopoulos, D., Hirsch, H.A., Struhl, K., An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139:4 (2009), 693–706.
44. Popivanova, B.K., Kitamura, K., Wu, Y., Kondo, T., Kagaya, T., Kaneko, S., et al. Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J. Clin. Invest. 118:2 (2008), 560–570.
45. Greten, F.R., Eckmann, L., Greten, T.F., Park, J.M., Li, Z.W., Egan, L.J., et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:3 (2004), 285–296.
46. Becker, C., Fantini, M.C., Schramm, C., Lehr, H.A., Wirtz, S., Nikolaev, A., et al. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21:4 (2004), 491–501.
47. Bollrath, J., Greten, F.R., IKK/NF-κB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep. 10:12 (2009), 1314–1319.
48. Grivennikov, S., Karin, E., Terzic, J., Mucida, D., Yu, G.Y., Vallabhapurapu, S., et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15:2 (2009), 103–113.
49. Pikarsky, E., Porat, R.M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:7007 (2004), 461–466.
50. Maeda, S., Kamata, H., Luo, J.L., Leffert, H., Karin, M., IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121:7 (2005), 977–990.
51. Sakurai, T., Maeda, S., Chang, L., Karin, M., Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc. Natl. Acad. Sci. U S A. 103 (2006), 10544–10551.
52. Luedde, T., Beraza, N., Kotsikoris, V., van Loo, G., Nenci, A., De Vos, R., et al. Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 11 (2007), 119–132.
53. Naugler, W.E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkawy, A.M., et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317:5834 (2007), 121–124.
54. Wong, V.W., Yu, J., Cheng, A.S., Wong, G.L., Chan, H.Y., Chu, E.S., et al. High serum interleukin-6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B. Int. J. Cancer 124:12 (2009), 2766–2770.
55. Shibata, W., Takaishi, S., Muthupalani, S., Pritchard, D.M., Whary, M.T., Rogers, A.B., et al. Conditional deletion of IkappaB-kinase-beta accelerates helicobacter-dependent gastric apoptosis, proliferation, and preneoplasia. Gastroenterology 138:3 (2010), 1022–1034 (e1-10).
56. Tu, S., Bhagat, G., Cui, G., Takaishi, S., Kurt-Jones, E.A., Rickman, B., et al. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14:5 (2008), 408–419.
57. Takahashi, H., Ogata, H., Nishigaki, R., Broide, D.H., Karin, M., Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell 17:1 (2010), 89–97.
58. Chow, A., Zhou, W., Liu, L., Fong, M.Y., Champer, J., Van Haute, D., et al. Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-κB. Sci. Rep., 4, 2014, 5750.
59. Mosser, D.M., Edwards, J.P., Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8:12 (2008), 958–969.
60. Jakubzick, C.V., Randolph, G.J., Henson, P.M., Monocyte differentiation and antigen-presenting functions. Nat. Rev. Immunol. 17:6 (2017), 349–362.
61. Biswas, S.K., Mantovani, A., Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11:10 (2010), 889–896.
62. Mantovani, A., Sozzani, S., Locati, M., Allavena, P., Sica, A., Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 23:11 (2002), 549–555.
63. Movahedi, K., Laoui, D., Gysemans, C., Baeten, M., Stangé, G., Van den Bossche, J., et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 70:14 (2010), 5728–5739.
64. Lin, E.Y., Nguyen, A.V., Russell, R.G., Pollard, J.W., Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 193 (2001), 727–740.
65. Hagemann, T., Biswas, S.K., Lawrence, T., Sica, A., Lewis, C.E., Regulation of macrophage function in tumors: the multifaceted role of NF-kappaB. Blood 113:14 (2009), 3139–3146.
66. Bradford, J.W., Baldwin, A.S., IKK/Nuclear factor-kappaB and oncogenesis: roles in tumor-Initiating cells and in the tumor microenvironment. Adv. Cancer Res. 121 (2014), 125–145.
67. Mancino, A., Lawrence, T., Nuclear factor-kappaB and tumor-associated macrophages. Clin. Cancer Res. 16:3 (2010), 784–789.
68. Capece, D., Fischietti, M., Verzella, D., Gaggiano, A., Cicciarelli, G., Tessitore, A., et al. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. BioMed Res. Int., 2013, 2013, 187204.
69. Hagemann, T., Wilson, J., Kulbe, H., Li, N.F., Leinster, D.A., Charles, K., et al. Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J. Immunol. 175:2 (2005), 1197–1205.
70. Hagemann, T., Wilson, J., Burke, F., Kulbe, H., Li, N.F., Plüddemann, A., et al. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J. Immunol. 176:8 (2006), 5023–5032.
71. Hagemann, T., Lawrence, T., McNeish, I., Charles, K.A., Kulbe, H., Thompson, R.G., et al. Re-educating tumor associated macrophages by targeting NF-κB. J. Exp. Med. 205 (2008), 1261–1268.
72. Saccani, A., Schioppa, T., Porta, C., Biswas, S.K., Nebuloni, M., Vago, L., et al. p50 nuclear factor-kappaB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res. 66:23 (2006), 11432–11440.
73. Chittezhath, M., Dhillon, M.K., Lim, J.Y., Laoui, D., Shalova, I.N., Teo, Y.L., et al. Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity 41:5 (2014), 815–829.
74. Disis, M.L., Immune regulation of cancer. J. Clin. Oncol. 28:29 (2010), 4531–4538.
75. Fridman, W.H., Galon, J., Pagès, F., Tartour, E., Sautès-Fridman, C., Kroemer, G., Prognostic and predictive impact of intra- and peritumoral immune infiltrates. Cancer Res. 71:17 (2011), 5601–5605.
76. Hopewell, E.L., Zhao, W., Fulp, W.J., Bronk, C.C., Lopez, A.S., Massengill, M., et al. Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance. J. Clin. Invest. 123:6 (2013), 2509–2522.
77. Zaynagetdinov, R., Stathopoulos, G.T., Sherrill, T.P., Cheng, D.S., McLoed, A.G., Ausborn, J.A., et al. Epithelial nuclear factor-κB signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes. Oncogene 31:26 (2012), 3164–3176.
78. Malaquin, N., Martinez, A., Rodier, F., Keeping the senescence secretome under control: molecular reins on the senescence-associated secretory phenotype. Exp. Gerontol. 82 (2016), 39–49.
79. Campisi, J., d'Adda di Fagagna, F., Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8 (2007), 729–740.
80. Lasry, A., Ben-Neriah, Y., Senescence-associated inflammatory responses: aging and cancer perspectives. Trends Immunol. 36:4 (2015), 217–228.
81. Kuilman, T., Peeper, D.S., Senescence-messaging secretome: SMS-ing cellular stress. Nat. Rev. Cancer 9:2 (2009), 81–94.
82. Toso, A., Revandkar, A., Di Mitri, D., Guccini, I., Proietti, M., Sarti, M., et al. Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep. 9:1 (2014), 75–89.
83. Wiley, C.D., Velarde, M.C., Lecot, P., Liu, S., Sarnoski, E.A., Freund, A., et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab. 23:2 (2016), 303–314.
84. Eggert, T., Wolter, K., Ji, J., Ma, C., Yevsa, T., Klotz, S., et al. Distinct functions of senescence-Associated immune responses in liver tumor surveillance and tumor progression. Cancer Cell 30:4 (2016), 533–547.
85. Acosta, J.C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J.P., et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15:8 (2013), 978–990.
86. Chen, H., Ruiz, P.D., McKimpson, W.M., Novikov, L., Kitsis, R.N., Gamble, M.J., MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-Associated secretory phenotype. Mol. Cell 59:5 (2015), 719–731.
87. Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C.J., et al. mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat. Cell Biol. 17:9 (2015), 1205–1217.
88. Xue, W., Zender, L., Miething, C., Dickins, R.A., Hernando, E., Krizhanovsky, V., et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445:7128 (2007), 656–660.
89. Ventura, A., Kirsch, D.G., McLaughlin, M.E., Tuveson, D.A., Grimm, J., Lintault, L., et al. Restoration of p53 function leads to tumour regression in vivo. Nature 445:7128 (2007), 661–665.
90. Kang, T.W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479:7374 (2011), 547–551.
91. Iannello, A., Thompson, T.W., Ardolino, M., Lowe, S.W., Raulet, D.H., p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J. Exp. Med. 210:10 (2013), 2057–2069.
92. Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D.F., Bolden, J.E., et al. Non-cell-autonomous tumor suppression by p53. Cell 153:2 (2013), 449–460.
93. Rodier, F., Campisi, J., Four faces of cellular senescence. J. Cell Biol. 192:4 (2011), 547–556.
94. Liu, S., Uppal, H., Demaria, M., Desprez, P.Y., Campisi, J., Kapahi, P., Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Sci. Rep., 5, 2015, 17895.
95. Malaquin, N., Vercamer, C., Bouali, F., Martien, S., Deruy, E., Wernert, N., et al. Senescent fibroblasts enhance early skin carcinogenic events via a paracrine MMP-PAR-1 axis. PLoS One, 8(5), 2013, e63607.
96. Laberge, R.M., Awad, P., Campisi, J., Desprez, P.Y., Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron. 5:1 (2012), 39–44.
97. Laberge, R.M., Sun, Y., Orjalo, A.V., Patil, C.K., Freund, A., Zhou, L., et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat. Cell Biol. 17:8 (2015), 1049–1061.
98. Kelly, J., Ali Khan, A., Yin, J., Ferguson, T.A., Apte, R.S., Senescence regulates macrophage activation and angiogenic fate at sites of tissue injury in mice. J. Clin. Invest. 117:11 (2007), 3421–3426.
99. Sun, Y., Campisi, J., Higano, C., Beer, T.M., Porter, P., Coleman, I., et al. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat. Med. 18:9 (2012), 1359–1368.
100. Rielland, M., Cantor, D.J., Graveline, R., Hajdu, C., Mara, L., Diaz Bde, D., et al. Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression. J. Clin. Invest. 124:5 (2014), 2125–2135.
101. Yoshimoto, S., Loo, T.M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499:7456 (2013), 97–101.
102. Pribluda, A., Elyada, E., Wiener, Z., Hamza, H., Goldstein, R.E., Biton, M., et al. A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism. Cancer Cell 24:2 (2013), 242–256.
103. Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J.E., et al. Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. Genes Dev. 25:20 (2011), 2125–2136.
104. Freund, A., Patil, C.K., Campisi, J., p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 30:8 (2011), 1536–1548.
105. Ohanna, M., Giuliano, S., Bonet, C., Imbert, V., Hofman, V., Zangari, J., et al. Senescent cells develop a PARP-1 and nuclear factor-{kappa}B-associated secretome (PNAS). Genes Dev. 25:12 (2011), 1245–1261.
106. Rovillain, E., Mansfield, L., Caetano, C., Alvarez-Fernandez, M., Caballero, O.L., Medema, R.H., et al. Activation of nuclear factor-kappa B signalling promotes cellular senescence. Oncogene 30:20 (2011), 2356–2366.
107. Macià, A., Vaquero, M., Gou-Fàbregas, M., Castelblanco, E., Valdivielso, J.M., Anerillas, C., et al. Sprouty1 induces a senescence-associated secretory phenotype by regulating NFàB activity: implications for tumorigenesis. Cell Death Differ. 21:2 (2014), 333–343.
108. Salminen, A., Kauppinen, A., Kaarniranta, K., Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP). Cell. Signal. 24:4 (2012), 835–845.
109. Elkon, R., Rashi-Elkeles, S., Lerenthal, Y., Linhart, C., Tenne, T., Amariglio, N., et al. Dissection of a DNA-damage-induced transcriptional network using a combination of microarrays, RNA interference and computational promoter analysis. Genome Biol., 6(5), 2005, R43.
110. Kang, C., Xu, Q., Martin, T.D., Li, M.Z., Demaria, M., Aron, L., et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science, 349(6255), 2015, aaa5612.
111. Liu, F., Wu, S., Ren, H., Gu, J., Klotho suppresses RIG-I-mediated senescence-associated inflammation. Nat. Cell Biol. 13:3 (2011), 254–262.
112. Alspach, E., Flanagan, K.C., Luo, X., Ruhland, M.K., Huang, H., Pazolli, E., et al. p38MAPK plays a crucial role in stromal-mediated tumorigenesis. Cancer Discov. 4:6 (2014), 716–729.
113. Chew, J., Biswas, S., Shreeram, S., Humaidi, M., Wong, E.T., Dhillion, M.K., et al. WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat. Cell Biol. 11:5 (2009), 659–666.
114. Nikolova-Karakashian, M., Karakashian, A., Rutkute, K., Role of neutral sphingomyelinases in aging and inflammation. Subcell. Biochem. 49 (2008), 469–486.
115. Orjalo, A.V., Bhaumik, D., Gengler, B.K., Scott, G.K., Campisi, J., Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc. Natl. Acad. Sci. U. S. A. 106:40 (2009), 17031–17036.
116. Mao, R., Fan, Y., Mou, Y., Zhang, H., Fu, S., Yang, J., TAK1 lysine 158 is required for TGF-β-induced TRAF6-mediated smad-independent IKK/NF-κB and JNK/AP-1 activation. Cell. Signal. 23:1 (2011), 222–227.
117. Dodeller, F., Gottar, M., Huesken, D., Iourgenko, V., Cenni, B., The lysosomal transmembrane protein 9 B regulates the activity of inflammatory signaling pathways. J. Biol. Chem. 283:31 (2008), 21487–21494.
118. Davalos, A.R., Kawahara, M., Malhotra, G.K., Schaum, N., Huang, J., Ved U: p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J. Cell Biol. 201:4 (2013), 613–629.
119. Taganov, K.D., Boldin, M.P., Chang, K.J., Baltimore, D., NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. U. S. A. 103:33 (2006), 12481–12486.
120. Olivieri, F., Albertini, M.C., Orciani, M., Ceka, A., Cricca, M., Procopio, A.D., Bonafè, M., DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging. Oncotarget 6:34 (2015), 35509–35521.
121. Bhaumik, D., Scott, G.K., Schokrpur, S., Patil, C.K., Orjalo, A.V., Rodier, F., et al. MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging (Albany NY) 1:4 (2009), 402–411.
122. Hayakawa, T., Iwai, M., Aoki, S., Takimoto, K., Maruyama, M., Maruyama, W., Motoyama, N., SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. PLoS One, 10(1), 2015, e0116480.
123. Yeung, F., Hoberg, J.E., Ramsey, C.S., Keller, M.D., Jones, D.R., Frye, R.A., Mayo, M.W., Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23:12 (2004), 2369–2380.
124. Pazolli, E., Alspach, E., Milczarek, A., Prior, J., Piwnica-Worms, D., Stewart, S.A., Chromatin remodeling underlies the senescence-associated secretory phenotype of tumor stromal fibroblasts that supports cancer progression. Cancer Res. 72:9 (2012), 2251–2261.