Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

Gambhir, S; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

doi:10.3748/wjg.v21.i11.3174

Cited by 101 publications

(73 citation statements)

References 88 publications

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“…43 Several studies have demonstrated an active NF-κB signaling pathway in CRC and linked the dysregulated NF-κB signaling pathway in colorectal tissue to the malignant transformation, tumor cell proliferation, anti-apoptosis, invasion/metastasis, angiogenesis, and therapeutic resistance. 41,[44][45][46] Evidence indicates that the NF-κB signaling pathway mediates these cellular processes through activation of its target genes comprising numerous growth factors, chemokines and cytokines, c-Myc, cyclin D1, cIAPs, and Bcl-2 family of proteins. Interestingly, the evidence presented by Kim et al 40 that gal-4 regulates NF-κB signaling and the expression of IL-6 in CRC cells lends strong support to our observations presented here that surface-bound gal-4 regulates NF-κB signaling pathway in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

“…The nuclear factor (NF)-kappaB (NF-κB) is an important transcriptional factor in the body homeostasis including the maintenance of innate immunity and controlling inflammation, 41,42 and its aberrant regulation is recognized in many human cancers. 43 Several studies have demonstrated an active NF-κB signaling pathway in CRC and linked the dysregulated NF-κB signaling pathway in colorectal tissue to the malignant transformation, tumor cell proliferation, anti-apoptosis, invasion/metastasis, angiogenesis, and therapeutic resistance.…”

Section: Discussionmentioning

confidence: 99%

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Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

Rao

2017

Tumour Biol.

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One long-term complication of chronic intestinal inflammation is the development of colorectal cancer. However, the mechanisms linking inflammation to the colorectal tumorigenesis are poorly defined. Previously, we have demonstrated that galectin-4 is predominantly expressed in the luminal epithelia of the gastrointestinal tract, and its loss of expression plays a key role in the colorectal tumorigenesis. However, the mechanism by which galectin-4 regulates inflammation-induced tumorigenesis is unclear. Here, we show that galectin-4 secreted by the colorectal cancer cell lines was bound to the cell surface. Neutralization of surface-bound galectin-4 with anti-galectin-4 antibody resulted in increased cell proliferation with concomitant secretion of several chemokines into the extracellular medium. Neutralization of the surface-bound galectin-4 also resulted in the up-regulation of transcription of 29 genes, several of which are components of multiple inflammation signaling pathways. In an alternate experiment, binding of recombinant galectin-4 protein to cell surface of the galectin-4-negative colorectal cancer cells resulted in increased p27, and decreased cyclin D1 and c-Myc levels, leading to cell cycle arrest and apoptosis. Together, these data demonstrated that surface-bound galectin-4 is a dual function protein—down-regulating cell proliferation and chemokine secretion in galectin-4-expressing colorectal cancer cells on one hand and inducing apoptosis in galectin-4-negative colorectal cancer cells on the other hand.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

Rao

2017

Tumour Biol.

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“…It consists of five homologous Rel homology domains (RHD), namely, Rel (p65), RelB, CRel (REI), p50, and p52. 15 Classic NF-κB is a dimer of p50 and p65. 16,17 In an unstimulated state, NF-κB is bound to the inhibitory proteins of the inhibitor of κB (IκB) family by the RHD in the cytoplasm.…”

mentioning

confidence: 99%

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening

Deng¹,

Jin²,

Wang³

et al. 2017

IJN

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Aseptic loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of prosthesis loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic prosthesis loosening.

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“…56 This is most likely due to the fact that NF-κB has been implicated in all the essential steps/processes that drive efficient tumorigenesis. 57 NF-κB has more than hundreds of validated transcriptional targets (http://www.bu.edu/nf-kb/gene-resources/target-genes/), out of which some of them are key players in determining the ability of cancer cells to indefinitely proliferate (cMyc and cyclin D1), inhibit apoptotic signals (ciAPS, c-FLP, and members of the bcl-2 family), migrate (IL-8), undergo angiogenesis (vascular endothelial growth factor (VEGF)) and undergo invasion/metastasis (matrix metalloproteinase (MMP)-2/9)).…”

Section: Nf-κb/relmentioning

confidence: 99%

“…57 NF-κB has more than hundreds of validated transcriptional targets (http://www.bu.edu/nf-kb/gene-resources/target-genes/), out of which some of them are key players in determining the ability of cancer cells to indefinitely proliferate (cMyc and cyclin D1), inhibit apoptotic signals (ciAPS, c-FLP, and members of the bcl-2 family), migrate (IL-8), undergo angiogenesis (vascular endothelial growth factor (VEGF)) and undergo invasion/metastasis (matrix metalloproteinase (MMP)-2/9)). 56,58 Tumor cells achieve constitutive activation of NF-κB by mutations in genes encoding the NF-κB transcription factors themselves or in genes that control NF-κB activity (such as IκB genes). Alternatively, the tumor cells can overexpress growth factors/inflammatory ligands which can induce NF-κB activation.…”

Section: Nf-κb/relmentioning

confidence: 99%

Molecular interplay of pro-inflammatory transcription factors and non-coding RNAs in esophageal squamous cell carcinoma

Sundaram

Bramhachari

2017

Tumour Biol.

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Esophageal squamous cell carcinoma is the sixth most common cancer in the developing world. The aggressive nature of esophageal squamous cell carcinoma, its tendency for relapse, and the poor survival prospects of patients diagnosed at advanced stages, represent a pressing need for the development of new therapies for this disease. Chronic inflammation is known to have a causal link to cancer pre-disposition. Nuclear factor kappa B and signal transducer and activator of transcription 3 are transcription factors which regulate immunity and inflammation and are emerging as key regulators of tumor initiation, progression, and metastasis. Although these pro-inflammatory factors in esophageal squamous cell carcinoma have been well-characterized with reference to protein-coding targets, their functional interactions with noncoding RNAs have only recently been gaining attention. Non-coding RNAs, especially microRNAs and long non-coding RNAs demonstrate potential as biomarkers and alternative therapeutic targets. In this review, we summarize the recent literature and concepts on non-coding RNAs that are regulated by/regulate nuclear factor kappa B and signal transducer and activator of transcription 3 in esophageal cancer progression. We also discuss how these recent discoveries can pave way for future therapeutic options to treat esophageal squamous cell carcinoma.

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Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

Cited by 101 publications

References 88 publications

Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening

Molecular interplay of pro-inflammatory transcription factors and non-coding RNAs in esophageal squamous cell carcinoma

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Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

Cited by 101 publications

References 88 publications

Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

Surface-bound galectin-4 regulates gene transcription and secretion of chemokines in human colorectal cancer cell lines

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-&kappa;B deacetylation in aseptic loosening

Molecular interplay of pro-inflammatory transcription factors and non-coding RNAs in esophageal squamous cell carcinoma

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The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening