Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 3  |  Page : 405-409

Nod-like receptor protein 3 inflammasome in head-and-neck cancer


Division of Cancer Research, Regional Cancer Centre, Laboratory of Molecular Medicine, Medical College, Thiruvananthapuram, Kerala, India

Date of Submission13-Dec-2018
Date of Acceptance13-May-2019
Date of Web Publication31-Jan-2020

Correspondence Address:
K Sheeja
Division of Cancer Research, Regional Cancer Centre, Laboratory of Molecular Medicine, Medical College, Thiruvananthapuram - 695 011, Kerala
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_849_18

Rights and Permissions
 > Abstract 


Activation of inflammasomes has a decisive role in host defense mechanism against pathogens and other intracellular risk factors, but recently, it has been revealed that they play a significant role in the pathogenesis of several diseases, including cancer. Nod-like receptor protein 3 (NLRP3) inflammasome, the best-studied inflammasome, has contrasting roles in cancer development and progressions. In head-and-neck cancers, the upregulated level of NLRP3 promotes tumor progression. The main objective of this review is to provide current knowledge on the involvement of NLRP3 inflammasome in head-and-neck cancers. Deeper understanding of the biology of this dynamic protein complex provides new scope for the development of more effective anticancer therapies.

Keywords: Head-and-neck cancer, inflammation, NRP3 inflammasome, pattern recognition receptors


How to cite this article:
Sheeja K, Lakshmi S. Nod-like receptor protein 3 inflammasome in head-and-neck cancer. J Can Res Ther 2020;16:405-9

How to cite this URL:
Sheeja K, Lakshmi S. Nod-like receptor protein 3 inflammasome in head-and-neck cancer. J Can Res Ther [serial online] 2020 [cited 2020 Sep 30];16:405-9. Available from: http://www.cancerjournal.net/text.asp?2020/16/3/405/277463




 > Introduction Top


Head-and-neck cancers are a heterogeneous group of diseases. They originate in the upper aerodigestive tract, including the oral cavity, larynx, pharynx, and nasopharynx, and are the sixth leading cancer worldwide. Head-and-neck cancers make up around 6% of all cancers. The major histological subtype within head-and-neck cancers is squamous cell carcinoma (HNSCC), arising from the epithelial membranes (mucus linings) of these regions. They are classified according to the part of the body in which they occur. The use of tobacco and alcohol is the most important risk factor for head-and-neck cancers.[1] Infection with high-risk factor human papillomavirus and genetic predisposition may also contribute toward the development of this malignancy.[2] Lung, mediastinal nodes, liver, and bone are the main sites of metastases.[3] The main treatment options for head-and-neck cancers are surgery, radiotherapy, and chemotherapy. Recent advances in the use of chemotherapy plus radiation and hyperfractionated radiotherapy has led to longer survival times in clinical trials affecting various sites, with different prognosis.[4] Treatment responses depend on many factors including stage of the disease.

The immune system plays a pivotal role in the development of malignancy. During the progression of tumor, an inflammatory microenvironment is created in the tumor vicinity that may accelerate the tumor growth into advanced stage.[5] Tumor microenvironment is comprised of proliferating tumor cells, stromal cells, blood cells, and infiltrating inflammatory cells, and they provide signals to regulate various events of tumor progression. Many types of cancers are etiologically linked to inflammation. As the tumor grows and proliferates, it activates innate immune cells and recruits effector cells to exert antitumor activity while promoting tumor progression through the production of pro-inflammatory molecules.[6],[7] Inflammatory cells in the microenvironment play an important role in providing mitogenic growth factors for proliferating tumors.[8] Chronic inflammation fuels the tumor growth by inducing genetic and epigenetic changes: DNA and tissue damage.[9] Inflammation is also orchestrated by a cytoplasmic multimeric protein complex known as inflammasomes. They provide a platform for caspase-1 activation which catalyzes the proteolytic cleavage and maturation of inactive interleukin (IL) IL-1β and IL-18 to their respective active forms. This is also accompanied by inflammatory cell death known as pyroptosis.[10] This might be involved in the suppression of tumors. Thus, inflammasomes play a crucial role in the progression or suppression of the developing tumor in a contextual manner based on cell type, tissue, and organ involved.[11] Experimental and clinical data indicate that the upregulation of nod-like receptor protein 3 (NLRP3) inflammasome in head-and-neck tumor is associated with the self-renewal activation of cancer stem cells.[12] In this review, we describe the recent research in the area of NLRP3 inflammasomes and head-and-neck malignancies.


 > Pattern Recognition Receptors Top


Pattern recognition receptors (PRRs) are germline-encoded receptors present on innate immune cells including dendritic cells, monocytes, macrophages, neutrophils, natural killer (NK) cells, and epithelial cells, which play a central role in the immune response. PRRs can be expressed on cell surfaces, in the cytoplasm, or in endosomes.[13] The host defense system of the body is activated when pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs) released from infected cells, tumors, and damaged tissues are recognized by cytosolic PRRs.[14] The PRR family consists of various members, including toll-like receptors (TLRs), nucleotide-binding and oligomerization domain NLRs, retinoic acid-inducible gene I-like receptors (RLRs), C-type lectins (CTL), and absent in melanoma (AIM)-like receptors (ALRs).[15],[16] Plasma membrane PRRs include TLRs and CTLs, whereas the NLRs, RLRs, and ALRs are intracellular in nature.[17] Recently, the NLR family has gained a lot of attention in cancer research due to its regulatory effect on inflammation and immunity. Studies have revealed that certain members of NLR proteins participate in inflammatory process through the formation of inflammasomes.


 > Nucleotide-Binding and Oligomerization Domain-Like Receptors Top


NLRs are located in the cytoplasm of immune-competent cells that recognize microbial products and DAMPs and activate the nuclear factor kappa B (NF-κB) complex, leading to the expression of pro-inflammatory and chemotactic cytokines. NLRs are classified into 22 isoforms in humans.[18] In general, NLRs display three domains, namely the C-terminal domain which contains a leucine-rich repeat (LRR), which is a sensing unit; the N-terminal which participates in protein–protein interaction; and the central region called NOD domain/NACHAT domain, which mediates NLR oligomerization. NLRs have been subdivided into five types based on the domain structure and evolutionary analysis. They are NLRA (acidic transactivation domain), NLRB (the baculoviral inhibitory repeat-like domain), NLRC (the caspase activation and recruitment domain), and NLRP (the pyrin domain), and NLRX (N-terminal mitochondria-targeting sequence). NLR family members take part in innate immune signaling through activation or inhibition of the inflammasome.[19] Among different NLRs, NLRP1, NLRP2, NLRP3, NLRC4, NLRP6, NLRP7, and NLRP 12, as well as the PYHIN family member AIM2, have been shown to form inflammasomes.[20],[21]


 > Nod-Like Receptor Protein 3 Inflammasome Top


The NLRP3 inflammasome was first identified by Tschopp in 2002 as a multiprotein complex containing CASP1, CASP5, Pycard/Asc, and NLR protein 1 (NLRP1). They are multicomplex proteins formed by the oligomerization of certain NLRs and serve as a central molecular platform for inflammatory reaction.[22] Recently, more than twenty inflammasomes have been identified, and NLRP3 inflammasome is composed of NLRP3; ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain) which is an adaptor protein encoded by PYCARD; and the precursor pro-caspase-1. NLRP3 has three domains, namely amino-terminal death-fold domain, carboxy-terminal LRRs, and a central NACHT nucleotide-binding domain.[14] The ASC consists of the following two death-fold domains: a pyrin domain and a caspase activation and recruitment domain (CARD). Procaspase-1 connects to NLRP3 via ASC. The association of NLRP3 with ASC is required for the recruitment of procaspase-1.[23],[24] Active caspase-1 converts pro-IL-1β and pro-IL-18 cytokines to active form. The active IL-1β recruits the native immune cells, whereas the active IL-18 induces interferon-γ and enhances the activity of T cells and NK cells.[25] In addition, IL-18 stimulates the expression of programmed death 1 (PD1) on NK cell, causes immunosuppression and promote metastases.[26]


 > Nod-Like Receptor Protein 3 Inflammasome Assembly And Activation Top


NLRP3 inflammasome uniquely requires a two-step mechanism for activation. First, a priming signal that involves the upregulation of NLRP3 expression induced by TLRs-NF-κB pathway and production of pro-IL-1 beta and pro-IL-18. Second signals include Reactive Oxygen Species (ROS), membrane perturbations, lysosomal destabilization, K+ efflux and extracellular ATP that promotes the oligomerization of NLRP3, ASC and procaspase-1 and leads to the formation of functional NLRP3 inflammasome complex. During this assembly, NLRP3 and ASC interact through their PYD domains while association of ASC with caspase I via CARD/ CARD interactions. The bipartite nature of ASC represents the core structure of the inflammasome. Finally, clustering of caspase 1 induces processing of pro-IL-1β and pro-IL-18 into their active form. Activation of caspase results not only in the release of active pro-inflammatory cytokines but also induces inflammatory cell death, called pyroptosis.[27],[28] Pyroptosis is characterized by cell membrane rupture brought about by cell swelling and lysis.[29] Hence, the event of pyroptosis and NLRP3 inflammasome may have important implications for the clinical development of anticancer therapeutics.


 > Dual Role Of Nod-Like Receptor Protein 3 Inflammasome In Cancer Top


NLRP3 inflammasome is probably the most versatile inflammasome subtype with diverse biologic and chemical agents. It is predominantly expressed in neutrophils, macrophages, monocytes, and conventional dendritic cells, and its expression is inducible in response to the inflammatory stimuli. The NLRP3 inflammasome regulates the initiation and progression and therapeutic responses of cancer. The interplay between malignant cells and inflammasome complex has a very contrasting role. It exerts procarcinogenic effect by suppressing NK and T cell–mediated anticancer activities. In addition, it stimulates the production of trophic factors that favours the development of secondary tumors. On other hand this protein complex produce anticancer effects through immunostimulation and inflammatory cell death.[30]


 > Nod-Like Receptor Protein 3 in Head -And -Neck Cancer Top


Head-and-neck squamous cell carcinoma (HNSCC) is an aggressive disease, and mortality from this disease remains high because of the development of distant metastases and poor prognosis. Surgery, chemotherapy, and radiotherapy are the most important treatment strategies and are used either alone or in combination to obtain complete remission and cure.[31] NLR is found to be involved in the progression of head-and-neck cancers. Oral cancer is the sixth-most prevalent malignancy in the world, and oral squamous cell carcinoma (OSCC) accounts for approximately 90% of all oral malignancies. Studies have suggested that IL-1β can be induced by tobacco and betel quid-related carcinogens, and it participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting the aggressiveness of OSCC.[32] Despite advances in therapy, which have improved the quality of life, survival rates of head-and-neck cancers have remained static for many years. The efficacy of immunotherapies is hampered in head-and-neck cancer due to immunosuppressive tumor microenvironment.[33],[34] HNSCC-related inflammation is characterized by increased pro-inflammatory cytokines and acute-phase reactant proteins (C-reactive protein, serum amyloid A protein) that enhance the recruitment of circulating neutrophils, monocytes, and myeloid-derived suppressor cells (MDSCs) while inhibiting the recruitment of lymphocytes to the circulation.[35] Clinical studies indicate that the NF-κB play a pivotal role in the carcinogenesis of HNSCC.[36] Owing to their ability to induce pro-inflammatory cytokines, TLR and other innate immune receptor signaling pathways, in the context of tumor initiation, progression, and metastasis, have attracted close attention in recent years.[37] In oral squamous cell carcinoma, lower expression of NLRP3 is related to less aggressiveness of the disease. Wang et al. in 2018 demonstrated that increased expression of NLRP3 in OSCC was associated with tumor growth and metastasis and the knockdown of NLRP3 inhibited the proliferation, migration, and invasion of OSCC cells in in vivo.[38] Recently, it has been identified that blocking NLRP3 inflammasome by MCC950 reduced IL1β, MDSCs, Tregs (regulatory T), and TAMs (tumor-associated macrophages), which directly correlated with the reduction of tumors.[39] NLRP3 inflammasome was elevated after receiving 5-fluorouracil (FU)-based chemotherapy both in patient sample and cell lines. It has been found that NLRP3 silencing significantly enhanced the proapoptosis effect of 5-FU and inhibited the proliferation in oral cancer cells. Detailed investigation revealed that 5-FU-mediated chemoresistance is by generating intracellular ROS and by the activation of NLRP3 inflammasome.[40]

The purinergic receptor P2X7 (P2X7R), a member of the P2XR subfamily, facilitates the metastasis of cancer cells. P2X7 is mainly expressed by monocytes, macrophages, as well as dendritic cells. During innate immune responses, activated PRRs induce ATP release, which in turn can activate P2X7 receptor. The NLRP3 inflammasome pathway is considered to be one of the most important P2X7R-induced downstream pathways.[41],[42] Prolonged activation of P2X7 creates nonselective pores on cell membranes, leading to cell death. Bae et al. demonstrated that HNSCC can produce active IL-1β via P2X7/NLRP3 inflammasome pathways and reduce the survival and invasiveness of HNSCC by blocking P2X7R/NLRP3 inflammasome.[43] Altogether, the downregulation of NLRP3 inflammasome may contribute to the development of novel therapeutic approaches or diagnostic markers predicting the prognosis and the degree of HNSCC malignancy. Downregulation of NLRP3 inflammasome has the potential to be a new therapeutic approach in head-and-neck cancer therapy.


 > Nod-Like Receptor Mutations In Head -And -Neck Cancer Top


A series of mutations are necessary for the malignant change which leads to an increased cell proliferation in potentially malignant disorders. Rapid advancement of genomic sequencing and high-throughput techniques has identified novel, targetable genes and genetic mutations in a variety of cancers.[44],[45] Mutational events reflect a high degree of genome instability, which is one of the hallmarks of cancer. In humans, there are 22 known NLRs, and the association of mutations and single-nucleotide polymorphisms (SNPs) in their genes with human diseases reflects their vital role in host defense.[46] Mutations in NLR genes are found to be associated with different types of cancers and are closely associated with higher degree of cancer genome instability. NLRP3 inflammasome polymorphism also exists in different types of cancers. An SNP in NLRP3 (rs35929419), in combination with CARD-8 polymorphism (rs2043211), has been associated with chronic inflammatory conditions.[47],[48] Lei et al. identified twenty novel NLRP mutations in HNSCC, and mutations in this group of genes were correlated with increased cancer cell genome mutation rates. These mutations were clustered at the LRR region of NLRP proteins, and the affected NLRP genes were mostly localized at chromosomes 11p15.4 and 19q13.42-19q13.43. This documented that NLRP3 inflammasome can be a potential therapeutic target and molecular biomarker of HNSCC genome instability.[49]


 > Conclusion Top


NLRP3 has emerged as a central regulator in the inflammatory process, and its activation directly correlates with the progression of head-and-neck tumors. However, very few studies have been done to explore the molecular mechanism behind cross talk between NLRP3 inflammasome and head-and-neck cancers. Further studies are required to unravel the molecular mechanisms behind the modulation of inflammasome and to determine their potential therapeutic role in head-and-neck cancers. The involvement of the NLRP3 inflammasome in head-and-neck cancers makes it a highly attractive drug target.

Acknowledgment

The authors would like to acknowledge Department of Biotechnology, Govt, of India for providing financial support.

Financial support and sponsorship

This study was financially supported by the Department of Biotechnology under BioCARe.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Dal Maso L, Torelli N, Biancotto E, Di Maso M, Gini A, Franchin G, et al. Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: A re-analysis of case-control studies using bi-dimensional spline models. Eur J Epidemiol 2016;31:385-93.  Back to cited text no. 1
    
2.
Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol 2015;33:3235-42.  Back to cited text no. 2
    
3.
Lefebvre JL. Current clinical outcomes demand new treatment options for SCCHN. Ann Oncol 2005;16 Suppl 6:vi7-vi12.  Back to cited text no. 3
    
4.
Budach W, Hehr T, Budach V, Belka C, Dietz K. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer 2006;6:28.  Back to cited text no. 4
    
5.
Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, et al. Role of tumor microenvironment in tumorigenesis. J Cancer 2017;8:761-73.  Back to cited text no. 5
    
6.
Munn DH, Bronte V. Immune suppressive mechanisms in the tumor microenvironment. Curr Opin Immunol 2016;39:1-6.  Back to cited text no. 6
    
7.
Hagerling C, Casbon AJ, Werb Z. Balancing the innate immune system in tumor development. Trends Cell Biol 2015;25:214-20.  Back to cited text no. 7
    
8.
Hanahan D, Coussens LM. Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell 2012;21:309-22.  Back to cited text no. 8
    
9.
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74.  Back to cited text no. 9
    
10.
Man SM, Kanneganti TD. Regulation of inflammasome activation. Immunol Rev 2015;265:6-21.  Back to cited text no. 10
    
11.
Karki R, Man SM, Kanneganti TD. Inflammasomes and cancer. Cancer Immunol Res 2017;5:94-9.  Back to cited text no. 11
    
12.
Huang CF, Chen L, Li YC, Wu L, Yu GT, Zhang WF, et al. NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma. J Exp Clin Cancer Res 2017;36:116.  Back to cited text no. 12
    
13.
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: Update on toll-like receptors. Nat Immunol 2010;11:373-84.  Back to cited text no. 13
    
14.
He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 2016;41:1012-21.  Back to cited text no. 14
    
15.
Kanneganti TD, Lamkanfi M, Núñez G. Intracellular NOD-like receptors in host defense and disease. Immunity 2007;27:549-59.  Back to cited text no. 15
    
16.
Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol 2005;17:1-4.  Back to cited text no. 16
    
17.
Motta V, Soares F, Sun T, Philpott DJ. NOD-like receptors: Versatile cytosolic sentinels. Physiol Rev 2015;95:149-78.  Back to cited text no. 17
    
18.
Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, et al. The NLR gene family: A standard nomenclature. Immunity 2008;28:285-7.  Back to cited text no. 18
    
19.
Saxena M, Yeretssian G. NOD-like receptors: Master regulators of inflammation and cancer. Front Immunol 2014;5:327.  Back to cited text no. 19
    
20.
Ciraci C, Janczy JR, Sutterwala FS, Cassel SL. Control of innate and adaptive immunity by the inflammasome. Microbes Infect 2012;14:1263-70.  Back to cited text no. 20
    
21.
Jo EK, Kim JK, Shin DM, Sasakawa C. Molecular mechanisms regulating NLRP3 inflammasome activation. Cell Mol Immunol 2016;13:148-59.  Back to cited text no. 21
    
22.
Martinon F, Mayor A, Tschopp J. The inflammasomes: Guardians of the body. Annu Rev Immunol 2009;27:229-65.  Back to cited text no. 22
    
23.
Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 2004;430:213-8.  Back to cited text no. 23
    
24.
Groslambert M, Py BF. Spotlight on the NLRP3 inflammasome pathway. J Inflamm Res 2018;11:359-74.  Back to cited text no. 24
    
25.
Barker BR, Taxman DJ, Ting JP. Cross-regulation between the IL-1β/IL-18 processing inflammasome and other inflammatory cytokines. Curr Opin Immunol 2011;23:591-7.  Back to cited text no. 25
    
26.
Terme M, Ullrich E, Aymeric L, Meinhardt K, Desbois M, Delahaye N, et al. IL-18 induces PD-1-dependent immunosuppression in cancer. Cancer Res 2011;71:5393-9.  Back to cited text no. 26
    
27.
Sutterwala FS, Haasken S, Cassel SL. Mechanism of NLRP3 inflammasome activation. Ann N Y Acad Sci 2014;1319:82-95.  Back to cited text no. 27
    
28.
Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol 2001;9:113-4.  Back to cited text no. 28
    
29.
Shi J, Gao W, Shao F. Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci 2017;42:245-54.  Back to cited text no. 29
    
30.
Zitvogel L, Kepp O, Galluzzi L, Kroemer G. Inflammasomes in carcinogenesis and anticancer immune responses. Nat Immunol 2012;13:343-51.  Back to cited text no. 30
    
31.
de Vita V, Lawrence TS, Rosenberg SA. Cancer: Principles & Practice of Oncology. 8th ed. Baltimore, MD, USA: Lippincott Williams & Wilkins; 2004.  Back to cited text no. 31
    
32.
Lee CH, Chang JS, Syu SH, Wong TS, Chan JY, Tang YC, et al. IL-1β promotes malignant transformation and tumor aggressiveness in oral cancer. J Cell Physiol 2015;230:875-84.  Back to cited text no. 32
    
33.
Tong CC, Kao J, Sikora AG. Recognizing and reversing the immunosuppressive tumor microenvironment of head and neck cancer. Immunol Res 2012;54:266-74.  Back to cited text no. 33
    
34.
Duray A, Demoulin S, Hubert P, Delvenne P, Saussez S. Immune suppression in head and neck cancers: A review. Clin Dev Immunol 2010;2010:701657.  Back to cited text no. 34
    
35.
Charles KA, Harris BD, Haddad CR, Clarke SJ, Guminski A, Stevens M, et al. Systemic inflammation is an independent predictive marker of clinical outcomes in mucosal squamous cell carcinoma of the head and neck in oropharyngeal and non-oropharyngeal patients. BMC Cancer 2016;16:124.  Back to cited text no. 35
    
36.
Yan M, Xu Q, Zhang P, Zhou XJ, Zhang ZY, Chen WT. Correlation of NF-kappaB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma. BMC Cancer 2010;10:437.  Back to cited text no. 36
    
37.
Newton K, Dixit VM. Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol 2012;4. pii: a006049.  Back to cited text no. 37
    
38.
Wang H, Luo Q, Feng X, Zhang R, Li J, Chen F. NLRP3 promotes tumor growth and metastasis in human oral squamous cell carcinoma. BMC Cancer 2018;18:500.  Back to cited text no. 38
    
39.
Chen L, Huang CF, Li YC, Deng WW, Mao L, Wu L, et al. Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma. Cell Mol Life Sci 2018;75:2045-58.  Back to cited text no. 39
    
40.
Feng X, Luo Q, Zhang H, Wang H, Chen W, Meng G, et al. The role of NLRP3 inflammasome in 5-fluorouracil resistance of oral squamous cell carcinoma. J Exp Clin Cancer Res 2017;36:81.  Back to cited text no. 40
    
41.
Franceschini A, Capece M, Chiozzi P, Falzoni S, Sanz JM, Sarti AC, et al. The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J 2015;29:2450-61.  Back to cited text no. 41
    
42.
Di Virgilio F. Liaisons dangereuses: P2X(7) and the inflammasome. Trends Pharmacol Sci 2007;28:465-72.  Back to cited text no. 42
    
43.
Bae JY, Lee SW, Shin YH, Lee JH, Jahng JW, Park K. P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer. Oncotarget 2017;8:48972-82.  Back to cited text no. 43
    
44.
Teer JK. An improved understanding of cancer genomics through massively parallel sequencing. Transl Cancer Res 2014;3:243-59.  Back to cited text no. 44
    
45.
Tuna M, Amos CI. Genomic sequencing in cancer. Cancer Lett 2013;340:161-70.  Back to cited text no. 45
    
46.
Zhong Y, Kinio A, Saleh M. Functions of NOD-like receptors in human diseases. Front Immunol 2013;4:333.  Back to cited text no. 46
    
47.
Verma D, Lerm M, Blomgran Julinder R, Eriksson P, Söderkvist P, Särndahl E. Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: Relation to common inflammatory diseases? Arthritis Rheum 2008;58:888-94.  Back to cited text no. 47
    
48.
Verma D, Särndahl E, Andersson H, Eriksson P, Fredrikson M, Jönsson JI, et al. The Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to excessive interleukin-1β and IL-18 production. PLoS One 2012;7:e34977.  Back to cited text no. 48
    
49.
Lei Y, Lui VW, Grandis JR, Egloff AM. Identification of mutations in the PYRIN-containing NLR genes (NLRP) in head and neck squamous cell carcinoma. PLoS One 2014;9:e85619.  Back to cited text no. 49
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Pattern Recognit...>Nucleotide-Bindi...>Nod-Like Recepto...>Nod-Like Recepto...>Dual Role Of Nod...>Nod-Like Recepto...>Nod-Like Recepto...>Conclusion
  In this article
>References

 Article Access Statistics
    Viewed1123    
    Printed273    
    Emailed0    
    PDF Downloaded267    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]