Hostname: page-component-5c6d5d7d68-wbk2r Total loading time: 0 Render date: 2024-08-15T10:26:55.415Z Has data issue: false hasContentIssue false

NF-κB: a mediator that promotes or inhibits angiogenesis in human diseases?

Published online by Cambridge University Press:  28 July 2023

Yijing Jiang
Affiliation:
Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
Jie Zhang
Affiliation:
Department of Oncology, Affiliated Tumor Hospital of Nantong University, 30Tongyang North Road, Pingchao Town, Nantong 226361, Jiangsu, People's Republic of China
Conglin Shi
Affiliation:
Department of Pathogenic Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
Xingjuan Li
Affiliation:
Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
Yongying Jiang
Affiliation:
Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
Renfang Mao*
Affiliation:
Department of Pathophysiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China
*
Corresponding author: Renfang Mao; Email: maorenfang@ntu.edu.cn

Abstract

The nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) signaling pathway, which is conserved in invertebrates, plays a significant role in human diseases such as inflammation-related diseases and carcinogenesis. Angiogenesis refers to the growth of new capillary vessels derived from already existing capillaries and postcapillary venules. Maintaining normal angiogenesis and effective vascular function is a prerequisite for the stability of organ tissue function, and abnormal angiogenesis often leads to a variety of diseases. It has been suggested that NK-κB signalling molecules under pathological conditions play an important role in vascular differentiation, proliferation, apoptosis and tumourigenesis by regulating the transcription of multiple target genes. Many NF-κB inhibitors are being tested in clinical trials for cancer treatment and their effect on angiogenesis is summarised. In this review, we will summarise the role of NF-κB signalling in various neovascular diseases, especially in tumours, and explore whether NF-κB can be used as an attack target or activation medium to inhibit tumour angiogenesis.

Type
Review
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

These authors made equal contributions to this work.

References

Sun, SC, Chang, JH and Jin, J (2013) Regulation of nuclear factor-κB in autoimmunity. Trends in Immunology 34, 282289.CrossRefGoogle ScholarPubMed
Bottex-Gauthier, C et al. (2002) [The Rel/NF-kappa-B transcription factors: complex role in cell regulation]. Pathologie-Biologie 50, 204211.CrossRefGoogle ScholarPubMed
Zhang, Q, Lenardo, MJ and Baltimore, D (2017) 30 Years of NF-κB: a blossoming of relevance to human pathobiology. Cell 168, 3757.CrossRefGoogle ScholarPubMed
Taniguchi, K and Karin, M (2018) NF-κB, inflammation, immunity and cancer: coming of age. Nature reviews. Immunology 18, 309324.CrossRefGoogle ScholarPubMed
Delgado, VM et al. (2011) Modulation of endothelial cell migration and angiogenesis: a novel function for the ‘tandem-repeat’ lectin galectin-8. FASEB Journal 25, 242254.CrossRefGoogle ScholarPubMed
Geudens, I and Gerhardt, H (2011) Coordinating cell behaviour during blood vessel formation. Development 138, 45694583.CrossRefGoogle ScholarPubMed
Polyak, K, Haviv, I and Campbell, IG (2009) Co-evolution of tumor cells and their microenvironment. Trends in Genetics: TIG 25, 3038.CrossRefGoogle ScholarPubMed
Polyak, K and Weinberg, RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nature Reviews. Cancer 9, 265273.CrossRefGoogle ScholarPubMed
Quail, DF and Joyce, JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nature Medicine 19, 14231437.CrossRefGoogle ScholarPubMed
Rehman, AO and Wang, CY (2006) Notch signaling in the regulation of tumor angiogenesis. Trends in Cell Biology 16, 293300.CrossRefGoogle ScholarPubMed
Fernández-Chacón, M et al. (2021) Role of Notch in endothelial biology. Angiogenesis 24, 237250.CrossRefGoogle ScholarPubMed
Zhou, W et al. (2021) Unraveling the molecular mechanisms between inflammation and tumor angiogenesis. American Journal of Cancer Research 11, 301317.Google ScholarPubMed
Noort, AR et al. (2014) NF-κB-inducing kinase is a key regulator of inflammation-induced and tumour-associated angiogenesis. The Journal of Pathology 234, 375385.CrossRefGoogle ScholarPubMed
Ashander, LM et al. (2016) Targeting endothelial adhesion molecule transcription for treatment of inflammatory disease: a proof-of-concept study. Mediators of Inflammation 2016, 7945848.CrossRefGoogle ScholarPubMed
Ghosh, G et al. (2012) NF-κB regulation: lessons from structures. Immunological Reviews 246, 3658.CrossRefGoogle ScholarPubMed
Smale, ST (2012) Dimer-specific regulatory mechanisms within the NF-κB family of transcription factors. Immunological Reviews 246, 193204.CrossRefGoogle ScholarPubMed
Neumann, M and Naumann, M (2007) Beyond IkappaBs: alternative regulation of NF-kappaB activity. FASEB Journal 21, 26422654.CrossRefGoogle ScholarPubMed
Mulero, MC et al. (2019) Genome reading by the NF-κB transcription factors. Nucleic Acids Research 47, 99679989.CrossRefGoogle ScholarPubMed
Ji, Z et al. (2019) Inflammatory regulatory network mediated by the joint action of NF-kB, STAT3, and AP-1 factors is involved in many human cancers. Proceedings of the National Academy of Sciences of the USA 116, 94539462.CrossRefGoogle ScholarPubMed
Schuster, M et al. (2013) Atypical IκB proteins – nuclear modulators of NF-κB signaling. Cell Communication and Signaling: CCS 11, 23.CrossRefGoogle ScholarPubMed
Sun, SC (2011) Non-canonical NF-κB signaling pathway. Cell Research 21, 7185.CrossRefGoogle ScholarPubMed
Karin, M and Greten, FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nature Reviews. Immunology 5, 749759.CrossRefGoogle ScholarPubMed
Majdalawieh, A and Ro, HS (2010) Regulation of IkappaBalpha function and NF-kappaB signaling: AEBP1 is a novel proinflammatory mediator in macrophages. Mediators of Inflammation 2010, 823821.CrossRefGoogle ScholarPubMed
Ferreiro, DU and Komives, EA (2010) Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha. Biochemistry 49, 15601567.CrossRefGoogle ScholarPubMed
Chen, LF and Greene, WC (2004) Shaping the nuclear action of NF-kappaB. Nature Reviews. Molecular Cell Biology 5, 392401.CrossRefGoogle ScholarPubMed
Israël, A (2010) The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harbor Perspectives in Biology 2, a000158.CrossRefGoogle ScholarPubMed
Vallabhapurapu, S and Karin, M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annual Review of Immunology 27, 693733.CrossRefGoogle ScholarPubMed
Ruland, J (2011) Return to homeostasis: downregulation of NF-κB responses. Nature Immunology 12, 709714.CrossRefGoogle ScholarPubMed
Rothwarf, DM and Karin, M (1999) The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus. Science's STKE: signal transduction knowledge environment 1999, RE1.CrossRefGoogle Scholar
May, MJ, Marienfeld, RB and Ghosh, S (2002) Characterization of the Ikappa B-kinase NEMO binding domain. The Journal of Biological Chemistry 277, 4599246000.CrossRefGoogle ScholarPubMed
Karin, M and Delhase, M (2000) The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. Seminars in Immunology 12, 8598.CrossRefGoogle ScholarPubMed
Zhang, T et al. (2021) NF-κB signaling in inflammation and cancer. MedComm 2, 618653.CrossRefGoogle ScholarPubMed
Pires, B et al. (2018) NF-kappaB: two sides of the same coin. Genes 9, 24.CrossRefGoogle ScholarPubMed
Cildir, G, Low, KC and Tergaonkar, V (2016) Noncanonical NF-κB signaling in health and disease. Trends in Molecular Medicine 22, 414429.CrossRefGoogle ScholarPubMed
Maubach, G et al. (2019) NF-kappaB-inducing kinase in cancer. Biochimica et biophysica acta. Reviews on Cancer 1871, 4049.CrossRefGoogle ScholarPubMed
Sun, SC (2012) The noncanonical NF-κB pathway. Immunological Reviews 246, 125140.CrossRefGoogle ScholarPubMed
Bonizzi, G and Karin, M (2004) The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends in Immunology 25, 280288.CrossRefGoogle ScholarPubMed
Vallabhapurapu, S et al. (2008) Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nature Immunology 9, 13641370.CrossRefGoogle Scholar
Senftleben, U et al. (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293, 14951499.CrossRefGoogle ScholarPubMed
Doebele, C et al. (2010) Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood 115, 49444950.CrossRefGoogle ScholarPubMed
Liu, LZ et al. (2011) MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS ONE 6, e19139.CrossRefGoogle ScholarPubMed
Tsoyi, K et al. (2010) PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3β/GATA-6 signaling pathways in TNF-α-activated human endothelial cells. Atherosclerosis 213, 115121.CrossRefGoogle ScholarPubMed
Sabatel, C et al. (2011) MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells. PLoS ONE 6, e16979.CrossRefGoogle ScholarPubMed
Zhu, N et al. (2011) Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration. Atherosclerosis 215, 286293.CrossRefGoogle ScholarPubMed
Ueda, R et al. (2009) Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proceedings of the National Academy of Sciences of the USA 106, 1074610751.CrossRefGoogle ScholarPubMed
Hu, G et al. (2010) miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes. American Journal of Physiology. Gastrointestinal and Liver Physiology 298, G542G550.CrossRefGoogle ScholarPubMed
Suárez, Y et al. (2007) Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circulation Research 100, 11641173.CrossRefGoogle ScholarPubMed
Poliseno, L et al. (2006) MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108, 30683071.CrossRefGoogle ScholarPubMed
Zhu, K et al. (2013) MiR-146a enhances angiogenic activity of endothelial cells in hepatocellular carcinoma by promoting PDGFRA expression. Carcinogenesis 34, 20712079.CrossRefGoogle ScholarPubMed
Cheng, HS et al. (2013) MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Molecular Medicine 5, 10171034.CrossRefGoogle ScholarPubMed
Sun, X et al. (2012) MicroRNA-181b regulates NF-κB-mediated vascular inflammation. The Journal of Clinical Investigation 122, 19731990.Google ScholarPubMed
Fasanaro, P et al. (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. The Journal of Biological Chemistry 283, 1587815883.CrossRefGoogle ScholarPubMed
Qi, J et al. (2012) microRNA-210 negatively regulates LPS-induced production of proinflammatory cytokines by targeting NF-κB1 in murine macrophages. FEBS Letters 586, 12011207.CrossRefGoogle ScholarPubMed
Maijer, KI et al. (2015) Nuclear factor-κB-inducing kinase Is expressed in synovial endothelial cells in patients with early arthritis and correlates with markers of inflammation: a prospective cohort study. The Journal of Rheumatology 42, 15731581.CrossRefGoogle Scholar
Madge, LA et al. (2008) Lymphotoxin-alpha 1 beta 2 and LIGHT induce classical and noncanonical NF-kappa B-dependent proinflammatory gene expression in vascular endothelial cells. The Journal of Immunology 180, 34673477.CrossRefGoogle ScholarPubMed
Brown, KD, Claudio, E and Siebenlist, U (2008) The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis. Arthritis Research & Therapy 10, 212.CrossRefGoogle ScholarPubMed
Tak, PP and Firestein, GS (2001) NF-kappaB: a key role in inflammatory diseases. The Journal of Clinical Investigation 107, 711.CrossRefGoogle ScholarPubMed
Suárez, Y et al. (2010) Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation. The Journal of Immunology 184, 2125.CrossRefGoogle ScholarPubMed
Tsai, YH et al. (2009) The M type K15 protein of Kaposi's sarcoma-associated herpesvirus regulates microRNA expression via its SH2-binding motif to induce cell migration and invasion. Journal of Virology 83, 622632.CrossRefGoogle Scholar
Wu, YH et al. (2011) The manipulation of miRNA-gene regulatory networks by KSHV induces endothelial cell motility. Blood 118, 28962905.CrossRefGoogle ScholarPubMed
Shan, SW et al. (2013) Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. Journal of Cell Science 126, 15171530.Google ScholarPubMed
Vrábel, D, Pour, L and Ševčíková, S (2019) The impact of NF-κB signaling on pathogenesis and current treatment strategies in multiple myeloma. Blood Reviews 34, 5666.CrossRefGoogle ScholarPubMed
Eluard, B et al. (2022) The alternative RelB NF-κB subunit is a novel critical player in diffuse large B-cell lymphoma. Blood 139, 384398.CrossRefGoogle ScholarPubMed
Lim, KH, Yang, Y and Staudt, LM (2012) Pathogenetic importance and therapeutic implications of NF-κB in lymphoid malignancies. Immunological Reviews 246, 359378.CrossRefGoogle ScholarPubMed
Courtois, G and Gilmore, TD (2006) Mutations in the NF-kappaB signaling pathway: implications for human disease. Oncogene 25, 68316843.CrossRefGoogle ScholarPubMed
Lake, A et al. (2009) Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases. International Journal of Cancer 125, 13341342.CrossRefGoogle Scholar
Kalaitzidis, D et al. (2002) The human B-cell lymphoma cell line RC-K8 has multiple genetic alterations that dysregulate the Rel/NF-kappaB signal transduction pathway. Oncogene 21, 87598768.CrossRefGoogle ScholarPubMed
Bredel, M et al. (2011) NFKBIA deletion in glioblastomas. The New England Journal of Medicine 364, 627637.CrossRefGoogle ScholarPubMed
Zheng, H et al. (2016) Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma. Proceedings of the National Academy of Sciences of the USA 113, 1128311288.CrossRefGoogle ScholarPubMed
Matthews, GM et al. (2016) NF-κB dysregulation in multiple myeloma. Seminars in Cancer Biology 39, 6876.CrossRefGoogle ScholarPubMed
Young, RM et al. (2019) Pathogenic B-cell receptor signaling in lymphoid malignancies: new insights to improve treatment. Immunological Reviews 291, 190213.CrossRefGoogle ScholarPubMed
Schmitz, R et al. (2018) Genetics and pathogenesis of diffuse large B-cell lymphoma. The New England Journal of Medicine 378, 13961407.CrossRefGoogle ScholarPubMed
Bhatt, D and Ghosh, S (2014) Regulation of the NF-κB-mediated transcription of inflammatory genes. Frontiers in Immunology 5, 71.CrossRefGoogle ScholarPubMed
Dawson, MA and Kouzarides, T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150, 1227.CrossRefGoogle ScholarPubMed
Patel, MB and Wang, J (2018) The identification and interpretation of cis-regulatory noncoding mutations in cancer. High-Throughput 8, 1.CrossRefGoogle ScholarPubMed
Lin, SC et al. (2006) Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers. Cancer Letters 243, 4754.CrossRefGoogle Scholar
Kang, S et al. (2005) Polymorphism in the nuclear factor kappa-B binding promoter region of cyclooxygenase-2 is associated with an increased risk of bladder cancer. Cancer Letters 217, 1116.CrossRefGoogle ScholarPubMed
Costa RM, DA et al. (2016) The NFκB signaling pathway in papillomavirus-induced lesions: friend or foe. Anticancer Research 36, 20732083.Google ScholarPubMed
Charostad, J et al. (2020) The interplay between EBV and KSHV viral products and NF-κB pathway in oncogenesis. Infectious Agents and Cancer 15, 62.CrossRefGoogle ScholarPubMed
Harhaj, EW and Giam, CZ (2018) NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma. The FEBS Journal 285, 33243336.CrossRefGoogle ScholarPubMed
Shokri, S et al. (2019) Complexity on modulation of NF-κB pathways by hepatitis B and C: a double-edged sword in hepatocarcinogenesis. Journal of Cellular Physiology 234, 1473414742.CrossRefGoogle Scholar
Gilmore, TD (2021) NF-κB and human cancer: what have we learned over the past 35 years. Biomedicines 9, 889.CrossRefGoogle ScholarPubMed
Gudkov, AV, Gurova, KV and Komarova, EA (2011) Inflammation and p53: a tale of two stresses. Genes & Cancer 2, 503516.CrossRefGoogle ScholarPubMed
Cerhan, JR et al. (2003) Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma. International Journal of Cancer 106, 784788.CrossRefGoogle ScholarPubMed
Becker, C et al. (2004) TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21, 491501.CrossRefGoogle ScholarPubMed
Bassères, DS et al. (2010) Requirement of the NF-kappaB subunit p65/RelA for K-Ras-induced lung tumorigenesis. Cancer Research 70, 35373546.CrossRefGoogle ScholarPubMed
Finco, TS et al. (1997) Oncogenic Ha-Ras-induced signaling activates NF-kappaB transcriptional activity, which is required for cellular transformation. The Journal of Biological Chemistry 272, 2411324116.CrossRefGoogle ScholarPubMed
Vazquez-Santillan, K et al. (2015) NF-κB signaling in cancer stem cells: a promising therapeutic target. Cellular Oncology 38, 327339.CrossRefGoogle ScholarPubMed
Yamamoto, M et al. (2013) NF-κB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype. Nature Communications 4, 2299.CrossRefGoogle ScholarPubMed
Vazquez-Santillan, K et al. (2016) NF-kappaΒ-inducing kinase regulates stem cell phenotype in breast cancer. Scientific Reports 6, 37340.CrossRefGoogle ScholarPubMed
Gonzalez-Torres, C et al. (2017) NF-κB participates in the stem cell phenotype of ovarian cancer cells. Archives of Medical Research 48, 343351.CrossRefGoogle ScholarPubMed
Sun, L et al. (2013) Epigenetic regulation of SOX9 by the NF-κB signaling pathway in pancreatic cancer stem cells. Stem Cells 31, 14541466.CrossRefGoogle ScholarPubMed
Liu, S et al. (2017) FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells. Oncotarget 8, 4469444704.CrossRefGoogle ScholarPubMed
Wang, D et al. (2015) Prostaglandin E2 promotes colorectal cancer stem cell expansion and metastasis in mice. Gastroenterology 149, 18841895, e4.CrossRefGoogle ScholarPubMed
Balkwill, F (2009) Tumour necrosis factor and cancer. Nature Reviews. Cancer 9, 361371.CrossRefGoogle ScholarPubMed
Grivennikov, SI and Karin, M (2011) Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Annals of the Rheumatic Diseases 70, i104i108.CrossRefGoogle ScholarPubMed
Taniguchi, K and Karin, M (2014) IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Seminars in Immunology 26, 5474.CrossRefGoogle ScholarPubMed
Chang, Q, Daly, L and Bromberg, J (2014) The IL-6 feed-forward loop: a driver of tumorigenesis. Seminars in Immunology 26, 4853.CrossRefGoogle Scholar
Meulmeester, E and Ten Dijke, P (2011) The dynamic roles of TGF-β in cancer. The Journal of Pathology 223, 205218.CrossRefGoogle ScholarPubMed
Grivennikov, SI, Greten, FR and Karin, M (2010) Immunity, inflammation, and cancer. Cell 140, 883899.CrossRefGoogle ScholarPubMed
Tan, MC et al. (2009) Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer. The Journal of Immunology 182, 17461755.CrossRefGoogle Scholar
Murooka, TT, Rahbar, R and Fish, EN (2009) CCL5 promotes proliferation of MCF-7 cells through mTOR-dependent mRNA translation. Biochemical and Biophysical Research Communications 387, 381386.CrossRefGoogle ScholarPubMed
Hagemann, T et al. (2008) ‘Re-educating’ tumor-associated macrophages by targeting NF-kappaB. The Journal of Experimental Medicine 205, 12611268.CrossRefGoogle ScholarPubMed
Karyampudi, L et al. (2016) PD-1 blunts the function of ovarian tumor-infiltrating dendritic cells by inactivating NF-κB. Cancer Research 76, 239250.CrossRefGoogle ScholarPubMed
Antonangeli, F et al. (2020) Regulation of PD-L1 expression by NF-κB in cancer. Frontiers in Immunology 11, 584626.CrossRefGoogle ScholarPubMed
Vivier, E et al. (2008) Functions of natural killer cells. Nature Immunology 9, 503510.CrossRefGoogle ScholarPubMed
Oh, H et al. (2017) An NF-κB transcription-factor-dependent lineage-specific transcriptional program promotes regulatory T cell identity and function. Immunity 47, 450465, e5.CrossRefGoogle ScholarPubMed
Isomura, I et al. (2009) c-Rel is required for the development of thymic Foxp3 + CD4 regulatory T cells. The Journal of Experimental Medicine 206, 30013014.CrossRefGoogle ScholarPubMed
Evaristo, C et al. (2016) Cutting edge: engineering active IKKβ in T cells drives tumor rejection. The Journal of Immunology 196, 29332938.CrossRefGoogle Scholar
Ward, JP, Gubin, MM and Schreiber, RD (2016) The role of neoantigens in naturally occurring and therapeutically induced immune responses to cancer. Advances in Immunology 130, 2574.CrossRefGoogle ScholarPubMed
Kalluri, R (2016) The biology and function of fibroblasts in cancer. Nature Reviews. Cancer 16, 582598.CrossRefGoogle ScholarPubMed
Koliaraki, V et al. (2017) Mesenchymal cells in colon cancer. Gastroenterology 152, 964979.CrossRefGoogle ScholarPubMed
Erez, N et al. (2010) Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell 17, 135147.CrossRefGoogle Scholar
Santolla, MF et al. (2018) miR-221 stimulates breast cancer cells and cancer-associated fibroblasts (CAFs) through selective interference with the A20/c-Rel/CTGF signaling. Journal of Experimental & Clinical Cancer Research: CR 37, 94.CrossRefGoogle ScholarPubMed
Greten, FR et al. (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118, 285296.CrossRefGoogle Scholar
Pikarsky, E et al. (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461466.CrossRefGoogle ScholarPubMed
Karin, M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441, 431436.CrossRefGoogle ScholarPubMed
DiDonato, JA, Mercurio, F and Karin, M (2012) NF-κB and the link between inflammation and cancer. Immunological Reviews 246, 379400.CrossRefGoogle ScholarPubMed
Joyce, D et al. (2001) NF-kappaB and cell-cycle regulation: the cyclin connection. Cytokine & Growth Factor Reviews 12, 7390.CrossRefGoogle ScholarPubMed
Kiraly, O et al. (2015) Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genetics 11, e1004901.CrossRefGoogle ScholarPubMed
Dutta, J et al. (2006) Current insights into the regulation of programmed cell death by NF-kappaB. Oncogene 25, 68006816.CrossRefGoogle ScholarPubMed
Gapuzan, ME, Yufit, PV and Gilmore, TD (2002) Immortalized embryonic mouse fibroblasts lacking the RelA subunit of transcription factor NF-kappaB have a malignantly transformed phenotype. Oncogene 21, 24842492.CrossRefGoogle ScholarPubMed
Gerondakis, S et al. (2014) NF-κB control of T cell development. Nature Immunology 15, 1525.CrossRefGoogle ScholarPubMed
Lin, L et al. (2019) Tertiary lymphoid organs in cancer immunology: mechanisms and the new strategy for immunotherapy. Frontiers in Immunology 10, 1398.CrossRefGoogle ScholarPubMed
Furtado, GC et al. (2007) Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. Proceedings of the National Academy of Sciences of the USA 104, 50265031.CrossRefGoogle ScholarPubMed
Luther, SA et al. (2002) Differing activities of homeostatic chemokines CCL19, CCL21, and CXCL12 in lymphocyte and dendritic cell recruitment and lymphoid neogenesis. The Journal of Immunology 169, 424433.CrossRefGoogle ScholarPubMed
Sautès-Fridman, C et al. (2019) Tertiary lymphoid structures in the era of cancer immunotherapy. Nature Reviews. Cancer 19, 307325.CrossRefGoogle ScholarPubMed
Carrà, G et al. (2020) P53 vs NF-κB: the role of nuclear factor-kappa B in the regulation of p53 activity and vice versa. Cellular and Molecular Life Sciences: CMLS 77, 44494458.CrossRefGoogle ScholarPubMed
Sakamoto, K et al. (2009) Constitutive NF-kappaB activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth. Clinical Cancer Research 15, 22482258.CrossRefGoogle Scholar
Lennikov, A et al. (2018) Selective IKK2 inhibitor IMD0354 disrupts NF-κB signaling to suppress corneal inflammation and angiogenesis. Angiogenesis 21, 267285.CrossRefGoogle ScholarPubMed
Shen, J et al. (2018) IL-17 induces macrophages to M2-like phenotype via NF-κB. Cancer Management and Research 10, 42174228.CrossRefGoogle ScholarPubMed
Dong, F et al. (2014) Dihydroartemisinin targets VEGFR2 via the NF-κB pathway in endothelial cells to inhibit angiogenesis. Cancer Biology & Therapy 15, 14791488.CrossRefGoogle ScholarPubMed
Mountain, DJ et al. (2007) Interleukin-1beta increases expression and activity of matrix metalloproteinase-2 in cardiac microvascular endothelial cells: role of PKCalpha/beta1 and MAPKs. American Journal of Physiology. Cell Physiology 292, C867C875.CrossRefGoogle ScholarPubMed
Popov, Y et al. (2006) Halofuginone induces matrix metalloproteinases in rat hepatic stellate cells via activation of p38 and NFkappaB. The Journal of Biological Chemistry 281, 1509015098.CrossRefGoogle ScholarPubMed
Ko, HM et al. (2005) Platelet-activating factor induces matrix metalloproteinase-9 expression through Ca(2+)- or PI3K-dependent signaling pathway in a human vascular endothelial cell line. FEBS Letters 579, 64516458.CrossRefGoogle ScholarPubMed
Martin, D, Galisteo, R and Gutkind, JS (2009) CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex. The Journal of Biological Chemistry 284, 60386042.CrossRefGoogle ScholarPubMed
Passaro, C et al. (2016) The oncolytic virus dl922-947 reduces IL-8/CXCL8 and MCP-1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma. Oncotarget 7, 15001515.CrossRefGoogle ScholarPubMed
Chen, L et al. (2018) Monocyte chemoattractant protein 1 and fractalkine play opposite roles in angiogenesis via recruitment of different macrophage subtypes. International Journal of Ophthalmology 11, 216222.Google ScholarPubMed
Chen, Y and Liu, J (2019) The prognostic roles of cyclooxygenase-2 for patients with basal cell carcinoma. Artificial Cells, Nanomedicine, and Biotechnology 47, 30533057.CrossRefGoogle ScholarPubMed
Luo, LH et al. (2020) Long non-coding RNA NKILA inhibited angiogenesis of breast cancer through NF-κB/IL-6 signaling pathway. Microvascular Research 129, 103968.CrossRefGoogle ScholarPubMed
Huang, S et al. (2001) Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene 20, 41884197.CrossRefGoogle ScholarPubMed
Pires, BR et al. (2017) NF-kappaB is involved in the regulation of EMT genes in breast cancer cells. PLoS ONE 12, e0169622.CrossRefGoogle ScholarPubMed
Scheel, C and Weinberg, RA (2012) Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Seminars in Cancer Biology 22, 396403.CrossRefGoogle ScholarPubMed
Huber, MA et al. (2004) NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. The Journal of Clinical Investigation 114, 569581.CrossRefGoogle Scholar
Malki, A et al. (2020) Molecular mechanisms of colon cancer progression and metastasis: recent insights and advancements. International Journal of Molecular Sciences 22, 130.CrossRefGoogle ScholarPubMed
Balkwill, F (2004) Cancer and the chemokine network. Nature Reviews. Cancer 4, 540550.CrossRefGoogle ScholarPubMed
Cummins, EP et al. (2006) Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proceedings of the National Academy of Sciences of the USA 103, 1815418159.CrossRefGoogle ScholarPubMed
Oliver, KM, Taylor, CT and Cummins, EP (2009) Hypoxia. Regulation of NFkappaB signalling during inflammation: the role of hydroxylases. Arthritis Research & Therapy 11, 215.CrossRefGoogle ScholarPubMed
Bonello, S et al. (2007) Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site. Arteriosclerosis, Thrombosis, and Vascular Biology 27, 755761.CrossRefGoogle Scholar
Frede, S et al. (2006) Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-kappaB. The Biochemical Journal 396, 517527.CrossRefGoogle ScholarPubMed
Jung, Y et al. (2003) Hypoxia-inducible factor induction by tumour necrosis factor in normoxic cells requires receptor-interacting protein-dependent nuclear factor kappa B activation. The Biochemical Journal 370, 10111017.CrossRefGoogle ScholarPubMed
He, K et al. (2014) Lipopolysaccharide-induced cross-tolerance against renal ischemia-reperfusion injury is mediated by hypoxia-inducible factor-2α-regulated nitric oxide production. Kidney International 85, 276288.CrossRefGoogle ScholarPubMed
Bellezza, I et al. (2018) Nrf2-Keap1 signaling in oxidative and reductive stress. Biochimica et biophysica acta. Molecular cell research 1865, 721733.CrossRefGoogle ScholarPubMed
Maines, MD (1997) The heme oxygenase system: a regulator of second messenger gases. Annual Review of Pharmacology and Toxicology 37, 517554.CrossRefGoogle ScholarPubMed
Rubiolo, JA, Mithieux, G and Vega, FV (2008) Resveratrol protects primary rat hepatocytes against oxidative stress damage: activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes. European Journal of Pharmacology 591, 6672.CrossRefGoogle ScholarPubMed
Józkowicz, A et al. (2003) Heme oxygenase and angiogenic activity of endothelial cells: stimulation by carbon monoxide and inhibition by tin protoporphyrin-IX. Antioxidants & Redox Signaling 5, 155162.CrossRefGoogle ScholarPubMed
Kisseleva, T et al. (2006) NF-kappaB regulation of endothelial cell function during LPS-induced toxemia and cancer. The Journal of Clinical Investigation 116, 29552963.CrossRefGoogle ScholarPubMed
Ricke-Hoch, M et al. (2020) In peripartum cardiomyopathy plasminogen activator inhibitor-1 is a potential new biomarker with controversial roles. Cardiovascular Research 116, 18751886.CrossRefGoogle ScholarPubMed
Ulfhammer, E et al. (2006) TNF-alpha mediated suppression of tissue type plasminogen activator expression in vascular endothelial cells is NF-kappaB- and p38 MAPK-dependent. Journal of Thrombosis and Haemostasis: JTH 4, 17811789.CrossRefGoogle ScholarPubMed
Rice, J et al. (2006) Molecular mediators of alphavbeta3-induced endothelial cell survival. Journal of Vascular Research 43, 422436.CrossRefGoogle ScholarPubMed
Jiang, Q et al. (2016) Lunasin suppresses the migration and invasion of breast cancer cells by inhibiting matrix metalloproteinase-2/-9 via the FAK/Akt/ERK and NF-κB signaling pathways. Oncology Reports 36, 253262.CrossRefGoogle ScholarPubMed
Liu, JF et al. (2018) Thrombospondin 2 promotes tumor metastasis by inducing matrix metalloproteinase-13 production in lung cancer cells. Biochemical Pharmacology 155, 537546.CrossRefGoogle ScholarPubMed
Yang, YL et al. (2004) Thrombospondin-1 mediates distal tubule hypertrophy induced by glycated albumin. The Biochemical Journal 379, 8997.CrossRefGoogle ScholarPubMed
Xiao, Q et al. (2005) Characterization of cis-regulatory elements of the vascular endothelial growth inhibitor gene promoter. The Biochemical Journal 388, 913920.CrossRefGoogle ScholarPubMed
Ho, FM et al. (2000) High glucose-induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH(2)-terminal kinase and caspase-3. Circulation 101, 26182624.CrossRefGoogle ScholarPubMed
Zhazykbayeva, S et al. (2020) The molecular mechanisms associated with the physiological responses to inflammation and oxidative stress in cardiovascular diseases. Biophysical Reviews 12, 947968.CrossRefGoogle ScholarPubMed
Chandrasekar, B et al. (2004) Activation of intrinsic and extrinsic proapoptotic signaling pathways in interleukin-18-mediated human cardiac endothelial cell death. The Journal of Biological Chemistry 279, 2022120233.CrossRefGoogle ScholarPubMed
Tadros, A et al. (2003) ABIN-2 protects endothelial cells from death and has a role in the antiapoptotic effect of angiopoietin-1. Blood 102, 44074409.CrossRefGoogle Scholar
Chng, HW et al. (2006) A new role for the anti-apoptotic gene A20 in angiogenesis. Experimental Cell Research 312, 28972907.CrossRefGoogle ScholarPubMed
Sabatel, C et al. (2010) Sprouty1, a new target of the angiostatic agent 16 K prolactin, negatively regulates angiogenesis. Molecular Cancer 9, 231.CrossRefGoogle ScholarPubMed
Migneault, F et al. (2020) Apoptotic exosome-like vesicles regulate endothelial gene expression, inflammatory signaling, and function through the NF-κB signaling pathway. Scientific Reports 10, 12562.CrossRefGoogle ScholarPubMed
Park, YA et al. (2014) Tumor suppressive effects of bromodomain-containing protein 7 (BRD7) in epithelial ovarian carcinoma. Clinical Cancer Research 20, 565575.CrossRefGoogle ScholarPubMed
Peng, C et al. (2007) BRD7 suppresses the growth of nasopharyngeal carcinoma cells (HNE1) through negatively regulating beta-catenin and ERK pathways. Molecular and Cellular Biochemistry 303, 141149.CrossRefGoogle ScholarPubMed
van Beijnum, JR et al. (2017) A genomic screen for angiosuppressor genes in the tumor endothelium identifies a multifaceted angiostatic role for bromodomain containing 7 (BRD7). Angiogenesis 20, 641654.CrossRefGoogle ScholarPubMed
Tromp, SC et al. (2000) Tumor angiogenesis factors reduce leukocyte adhesion in vivo. International Immunology 12, 671676.CrossRefGoogle ScholarPubMed
Luo, J et al. (1998) Angiostatin upregulates E-selectin in proliferating endothelial cells. Biochemical and Biophysical Research Communications 245, 906911.CrossRefGoogle ScholarPubMed
Dirkx, AE et al. (2006) Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB Journal 20, 621630.CrossRefGoogle ScholarPubMed
Yu, G et al. (2005) Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-kappaB-dependent manner. Blood 105, 35453551.CrossRefGoogle Scholar
Armulik, A, Genové, G and Betsholtz, C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Developmental Cell 21, 193215.CrossRefGoogle ScholarPubMed
Zuazo-Gaztelu, I and Casanovas, O (2018) Unraveling the role of angiogenesis in cancer ecosystems. Frontiers in Oncology 8, 248.CrossRefGoogle ScholarPubMed
Fraisl, P et al. (2009) Regulation of angiogenesis by oxygen and metabolism. Developmental Cell 16, 167179.CrossRefGoogle ScholarPubMed
Goel, S et al. (2011) Normalization of the vasculature for treatment of cancer and other diseases. Physiological Reviews 91, 10711121.CrossRefGoogle ScholarPubMed
Chen, ZJ et al. (2016) Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-κB signals. Molecular Oncology 10, 775788.CrossRefGoogle ScholarPubMed
Zhuang, SF et al. (2017) Atg7 regulates brain angiogenesis via NF-κB-dependent IL-6 production. International Journal of Molecular Sciences 18, 968.CrossRefGoogle ScholarPubMed
Ramadass, V, Vaiyapuri, T and Tergaonkar, V (2020) Small molecule NF-κB pathway inhibitors in clinic. International Journal of Molecular Sciences 21, 5164.CrossRefGoogle ScholarPubMed
Huang, JJ et al. (2014) Recent advances in the structure-based and ligand-based design of IKKβ inhibitors as anti-inflammation and anti-cancer agents. Current Medicinal Chemistry 21, 38933917.CrossRefGoogle ScholarPubMed
Liu, J et al. (2022) Ibrutinib inhibits angiogenesis and tumorigenesis in a BTK-independent manner. Pharmaceutics 14, 1876.CrossRefGoogle Scholar
Wang, X, Zhang, Z and Yao, C (2012) Bortezomib inhibits the angiogenesis mediated by mesenchymal stem cells. Cancer Investigation 30, 657662.CrossRefGoogle ScholarPubMed
Li, Y et al. (2015) Copper improves the anti-angiogenic activity of disulfiram through the EGFR/Src/VEGF pathway in gliomas. Cancer Letters 369, 8696.CrossRefGoogle ScholarPubMed
Gravina, GL et al. (2015) KPT-330, a potent and selective exportin-1 (XPO-1) inhibitor, shows antitumor effects modulating the expression of cyclin D1 and survivin [corrected] in prostate cancer models. BMC Cancer 15, 941.CrossRefGoogle ScholarPubMed
Singh, AK, Bishayee, A and Pandey, AK (2018) Targeting histone deacetylases with natural and synthetic agents: an emerging anticancer strategy. Nutrients 10, 731.CrossRefGoogle ScholarPubMed
Kunnumakkara, AB et al. (2008) Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappaB-regulated gene products. Clinical Cancer Research 14, 21282136.CrossRefGoogle ScholarPubMed
Chiang, IT et al. (2014) Curcumin synergistically enhances the radiosensitivity of human oral squamous cell carcinoma via suppression of radiation-induced NF-κB activity. Oncology Reports 31, 17291737.CrossRefGoogle ScholarPubMed
Li, J et al. (2015) Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C. Journal of Experimental & Clinical Cancer Research: CR 34, 46.CrossRefGoogle ScholarPubMed
Marquardt, JU et al. (2015) Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer. Journal of Hepatology 63, 661669.CrossRefGoogle ScholarPubMed
Li, Y and Zhang, T (2014) Targeting cancer stem cells by curcumin and clinical applications. Cancer Letters 346, 197205.CrossRefGoogle ScholarPubMed
Dhillon, N et al. (2008) Phase II trial of curcumin in patients with advanced pancreatic cancer. Clinical Cancer Research 14, 44914499.CrossRefGoogle ScholarPubMed
Anand, P et al. (2007) Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics 4, 807818.CrossRefGoogle ScholarPubMed
Long, Q et al. (2013) Induction of apoptosis and inhibition of angiogenesis by PEGylated liposomal quercetin in both cisplatin-sensitive and cisplatin-resistant ovarian cancers. Journal of Biomedical Nanotechnology 9, 965975.CrossRefGoogle ScholarPubMed
Lei, CS et al. (2018) Effects of quercetin combined with anticancer drugs on metastasis-associated factors of gastric cancer cells: in vitro and in vivo studies. The Journal of Nutritional Biochemistry 51, 105113.CrossRefGoogle ScholarPubMed
Huang, DY et al. (2018) Inhibition of EGF expression and NF-κB activity by treatment with quercetin leads to suppression of angiogenesis in nasopharyngeal carcinoma. Saudi Journal of Biological Sciences 25, 826831.CrossRefGoogle ScholarPubMed
Granado-Serrano, AB et al. (2010) Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells. Nutrition and Cancer 62, 390401.CrossRefGoogle ScholarPubMed
McCann, SE et al. (2005) Intakes of selected nutrients, foods, and phytochemicals and prostate cancer risk in western New York. Nutrition and Cancer 53, 3341.CrossRefGoogle ScholarPubMed
Nieman, DC et al. (2010) Quercetin's influence on exercise performance and muscle mitochondrial biogenesis. Medicine and Science in Sports and Exercise 42, 338345.CrossRefGoogle ScholarPubMed
Brito, AF et al. (2016) New approach for treatment of primary liver tumors: the role of quercetin. Nutrition and Cancer 68, 250266.CrossRefGoogle ScholarPubMed
Alvero, AB et al. (2009) Stem-like ovarian cancer cells can serve as tumor vascular progenitors. Stem Cells 27, 24052413.CrossRefGoogle ScholarPubMed
Huang, KF et al. (2014) Kallistatin, a novel anti-angiogenesis agent, inhibits angiogenesis via inhibition of the NF-κB signaling pathway. Biomedicine & pharmacotherapy = Biomédecine & Pharmacothérapie 68, 455461.CrossRefGoogle ScholarPubMed
Tabruyn, SP et al. (2005) The antiangiogenic factor, 16-kDa human prolactin, induces endothelial cell cycle arrest by acting at both the G0-G1 and the G2-M phases. Molecular Endocrinology 19, 19321942.CrossRefGoogle ScholarPubMed
Tabruyn, SP et al. (2003) The antiangiogenic factor 16K human prolactin induces caspase-dependent apoptosis by a mechanism that requires activation of nuclear factor-kappaB. Molecular Endocrinology 17, 18151823.CrossRefGoogle ScholarPubMed
Chen, YH et al. (2006) Anti-angiogenesis mediated by angiostatin K1-3, K1-4 and K1-4.5. Involvement of p53, FasL, AKT and mRNA deregulation. Thrombosis and Haemostasis 95, 668677.CrossRefGoogle ScholarPubMed
Hindler, K et al. (2006) The role of statins in cancer therapy. The Oncologist 11, 306315.CrossRefGoogle ScholarPubMed
Nakata, S et al. (2007) Statin treatment upregulates vascular neuronal nitric oxide synthase through Akt/NF-kappaB pathway. Arteriosclerosis, Thrombosis, and Vascular Biology 27, 9298.CrossRefGoogle ScholarPubMed
Gingras, D et al. (2004) Activation of tissue plasminogen activator gene transcription by Neovastat, a multifunctional antiangiogenic agent. Biochemical and Biophysical Research Communications 320, 205212.CrossRefGoogle ScholarPubMed
Simard, B et al. (2013) Shark cartilage extract induces cytokines expression and release in endothelial cells and induces E-selectin, plasminogen and t-PA genes expression through an antioxidant-sensitive mechanism. Cytokine 61, 104111.CrossRefGoogle ScholarPubMed
Escudier, B et al. (2007) Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941. The Journal of Urology 178, 19011905.CrossRefGoogle ScholarPubMed
Lu, C et al. (2010) Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. Journal of the National Cancer Institute 102, 859865.CrossRefGoogle ScholarPubMed
Loprinzi, CL et al. (2005) Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial. Cancer 104, 176182.CrossRefGoogle Scholar