NF-κB, an Active Player in Human Cancers
Tóm tắt
NF-κB comprises a family of five transcription factors that form distinct protein complexes, which bind to consensus DNA sequences at promoter regions of responsive genes regulating cellular processes. The past three decades have witnessed remarkable progress in understanding the NF-κB signaling pathway in physiologic and pathologic conditions. The role of NF-κB in human cancer initiation, development, metastasis, and resistance to treatment has drawn particular attention. A significant number of human cancers have constitutive NF-κB activity due to the inflammatory microenvironment and various oncogenic mutations. NF-κB activity not only promotes tumor cells' proliferation, suppresses apoptosis, and attracts angiogenesis, but it also induces epithelial–mesenchymal transition, which facilitates distant metastasis. In certain circumstances, NF-κB activation may also remodel local metabolism and anergize the immune system to favor tumor growth. Suppression of NF-κB in myeloid cells or tumor cells usually leads to tumor regression, which makes the NF-κB pathway a promising therapeutic target. However, because of its vital role in various biologic activities, components of the NF-κB pathway need to be carefully selected and evaluated to design targeted therapies. Cancer Immunol Res; 2(9); 823–30. ©2014 AACR.
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Tài liệu tham khảo
Sen, 1986, Multiple nuclear factors interact with the immunoglobulin enhancer sequences, Cell, 46, 705, 10.1016/0092-8674(86)90346-6
Gilmore, 1999, Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel, Oncogene, 18, 6925, 10.1038/sj.onc.1203222
Gilmore, 2004, The c-Rel transcription factor and B-cell proliferation: a deal with the devil, Oncogene, 23, 2275, 10.1038/sj.onc.1207410
Neri, 1991, B cell lymphoma–associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50, Cell, 67, 1075, 10.1016/0092-8674(91)90285-7
Greenman, 2007, Patterns of somatic mutation in human cancer genomes, Nature, 446, 153, 10.1038/nature05610
Pflueger, 2011, Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing, Genome Res, 21, 56, 10.1101/gr.110684.110
Boehm, 2007, Integrative genomic approaches identify IKBKE as a breast cancer oncogene, Cell, 129, 1065, 10.1016/j.cell.2007.03.052
Serhan, 2008, Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators, Nat Rev Immunol, 8, 349, 10.1038/nri2294
Terzic, 2010, Inflammation and colon cancer, Gastroenterology, 138, 2101, 10.1053/j.gastro.2010.01.058
Iliopoulos, 2009, An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation, Cell, 139, 693, 10.1016/j.cell.2009.10.014
Pikarsky, 2004, NF-kappaB functions as a tumour promoter in inflammation-associated cancer, Nature, 431, 461, 10.1038/nature02924
Gabrilovich, 2009, Myeloid-derived suppressor cells as regulators of the immune system, Nat Rev Immunol, 9, 162, 10.1038/nri2506
Long, 2009, Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor, Immunity, 31, 921, 10.1016/j.immuni.2009.09.022
Facciabene, 2012, T-regulatory cells: key players in tumor immune escape and angiogenesis, Cancer Res, 72, 2162, 10.1158/0008-5472.CAN-11-3687
Hagemann, 2008, “Re-educating” tumor-associated macrophages by targeting NF-kappaB, J Exp Med, 205, 1261, 10.1084/jem.20080108
Porta, 2009, Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB, Proc Natl Acad Sci U S A, 106, 14978, 10.1073/pnas.0809784106
Colotta, 2009, Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability, Carcinogenesis, 30, 1073, 10.1093/carcin/bgp127
Elinav, 2013, Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms, Nat Rev Cancer, 13, 759, 10.1038/nrc3611
Matsumoto, 2007, Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium, Nat Med, 13, 470, 10.1038/nm1566
Gerondakis, 2006, Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models, Oncogene, 25, 6781, 10.1038/sj.onc.1209944
Meylan, 2009, Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma, Nature, 462, 104, 10.1038/nature08462
Xia, 2012, Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model, Nat Cell Biol, 14, 257, 10.1038/ncb2428
Basseres, 2010, Requirement of the NF-kappaB subunit p65/RelA for K-Ras-induced lung tumorigenesis, Cancer Res, 70, 3537, 10.1158/0008-5472.CAN-09-4290
Forsythe, 1996, Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1, Mol Cell Biol, 16, 4604, 10.1128/MCB.16.9.4604
Huang, 2001, Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis, Oncogene, 20, 4188, 10.1038/sj.onc.1204535
John, 2001, The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis, Pathol Oncol Res, 7, 14, 10.1007/BF03032599
Kang, 2004, Epithelial-mesenchymal transitions: twist in development and metastasis, Cell, 118, 277, 10.1016/j.cell.2004.07.011
Li, 2012, Epithelial-mesenchymal transition induced by TNF-alpha requires NF-kappaB–mediated transcriptional upregulation of Twist1, Cancer Res, 72, 1290, 10.1158/0008-5472.CAN-11-3123
Wu, 2009, Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion, Cancer Cell, 15, 416, 10.1016/j.ccr.2009.03.016
Collins, 1995, Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers, FASEB J, 9, 899, 10.1096/fasebj.9.10.7542214
Nguyen, 2009, Metastasis: from dissemination to organ-specific colonization, Nat Rev Cancer, 9, 274, 10.1038/nrc2622
Hiratsuka, 2006, Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis, Nat Cell Biol, 8, 1369, 10.1038/ncb1507
Kawauchi, 2008, p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation, Nat Cell Biol, 10, 611, 10.1038/ncb1724
Kawauchi, 2009, Loss of p53 enhances catalytic activity of IKKbeta through O-linked beta-N-acetyl glucosamine modification, Proc Natl Acad Sci U S A, 106, 3431, 10.1073/pnas.0813210106
Mauro, 2011, NF-kappaB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration, Nat Cell Biol, 13, 1272, 10.1038/ncb2324
Barbie, 2009, Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1, Nature, 462, 108, 10.1038/nature08460
Chien, 2006, RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival, Cell, 127, 157, 10.1016/j.cell.2006.08.034
Bang, 2013, GSK-3alpha promotes oncogenic KRAS function in pancreatic cancer via TAK1-TAB stabilization and regulation of noncanonical NF-kappaB, Cancer Discov, 3, 690, 10.1158/2159-8290.CD-12-0541
Singh, 2012, TAK1 inhibition promotes apoptosis in KRAS-dependent colon cancers, Cell, 148, 639, 10.1016/j.cell.2011.12.033
Duran, 2008, The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis, Cancer Cell, 13, 343, 10.1016/j.ccr.2008.02.001
Ling, 2012, KrasG12D-induced IKK2/beta/NF-kappaB activation by IL-1alpha and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma., Cancer Cell, 21, 105, 10.1016/j.ccr.2011.12.006
Webster, 1999, Transcriptional cross talk between NF-kappaB and p53, Mol Cell Biol, 19, 3485, 10.1128/MCB.19.5.3485
Huang, 2007, Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB, Mol Cell, 26, 75, 10.1016/j.molcel.2007.02.019
Martin, 2005, Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3, Nat Immunol, 6, 777, 10.1038/ni1221
Giebler, 2000, p53 recruitment of CREB binding protein mediated through phosphorylated CREB: a novel pathway of tumor suppressor regulation, Mol Cell Biol, 20, 4849, 10.1128/MCB.20.13.4849-4858.2000
Xia, 2009, Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP, Proc Natl Acad Sci U S A, 106, 2629, 10.1073/pnas.0812256106
Tergaonkar, 2002, p53 stabilization is decreased upon NFkappaB activation: a role for NFkappaB in acquisition of resistance to chemotherapy, Cancer Cell, 1, 493, 10.1016/S1535-6108(02)00068-5
Cooks, 2013, Mutant p53 prolongs NF-kappaB activation and promotes chronic inflammation and inflammation-associated colorectal cancer, Cancer Cell, 23, 634, 10.1016/j.ccr.2013.03.022
Greten, 2004, IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer, Cell, 118, 285, 10.1016/j.cell.2004.07.013
Maeda, 2005, IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis, Cell, 121, 977, 10.1016/j.cell.2005.04.014
Luedde, 2007, Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma, Cancer Cell, 11, 119, 10.1016/j.ccr.2006.12.016
Dajee, 2003, NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia, Nature, 421, 639, 10.1038/nature01283
van Hogerlinden, 1999, Squamous cell carcinomas and increased apoptosis in skin with inhibited Rel/nuclear factor-kappaB signaling, Cancer Res, 59, 3299
Pham, 2004, Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species, Cell, 119, 529, 10.1016/j.cell.2004.10.017
Kamata, 2005, Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases, Cell, 120, 649, 10.1016/j.cell.2004.12.041
Keutgens, 2006, Deregulated NF-kappaB activity in haematological malignancies, Biochem Pharmacol, 72, 1069, 10.1016/j.bcp.2006.06.011
Greten, 2007, NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta, Cell, 130, 918, 10.1016/j.cell.2007.07.009
Xue, 2011, Response and resistance to NF-kappaB inhibitors in mouse models of lung adenocarcinoma, Cancer Discov, 1, 236, 10.1158/2159-8290.CD-11-0073
Wu, 2006, Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli, Science, 311, 1141, 10.1126/science.1121513
Wang, 1999, Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB, Nat Med, 5, 412, 10.1038/7410
Cusack, 2001, Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition, Cancer Res, 61, 3535
Bhat, 2013, Mesenchymal differentiation mediated by NF-kappaB promotes radiation resistance in glioblastoma, Cancer Cell, 24, 331, 10.1016/j.ccr.2013.08.001