Table 2.

NLRs and their emerging role in cancers

NLR	Synonyms	Cancer types	Interactions	References
NAIP	BIRC1; NLRB1; psiNAIP	Oral squamous cell carcinoma (SCC) Breast cancer Colon cancer (CC)	NAIP overexpression in SCC and breast cancer Increased NF-κB activation NAIP expression more in normal tissues in case of colon cancer	[78, 79] [83]
NLRP3	AII; AVP; FCU; MWS; FCAS; CIAS1; NALP3; C1orf7; CLR 1.1; Cryopyrin; CIAS1; PYPAF1; AGTAVPRL; NALP3	Hepatocellular carcinoma (HCC) Colorectal cancer Melanoma Gastric cancer Glioblastoma (GBM)	Plays protective role in HCC and colitis associated CRC NLRP3 constitutively expressed Enhanced NF-κB activation and positive IL-1 feedback loop is formed Promotes migration and tumor invasion Aberrant IL-1 expression in malignant glioma cells.	[38–43] [44] [45] [50, 51]
NLRP6	AVR; CLR 11.4; NALP6; NAVR; PYPAF5; NAVR/AVR; PAN3	Colitis associated Colorectal cancer	Acts as negative regulator of colorectal tumorigenesis Role of NLRP6 in self-renewal of intestinal epithelium Upregulation of SMARRC1 and Mycl1 (primarily expressed in epithelial cells) in Nlrp6 −/− mice	[88–91]
NLRP12	CLR 19.3; FCAS2; NALP12; RNO2; PYPAF7; PAN6; RNO; Monarch 1	Colitis associated colorectal cancer	Decreased inflammatory response by inhibition of NF-κB, ERK and STAT3 pathways Nlrp12 −/− mice are hypersusceptible to inflammation induced tumorigenesis	[164, 166]
NLRC4	CLR 2.1; CARD12; CLAN; CLAN1; CLANA; CLANB; CLANC; CLAND; Ipaf	Colitis associated colorectal cancer	Protective role of NLRC4 via caspase-1 mediated inflammasome formation Controls/inhibits epithelial cell and tumor cell proliferation	[63]
NLRP1	NALP1; CARD7	Inflammatory bowel disease and colitis-associated cancer	Protects against gastrointestinal inflammation and progression incolitis-induced tumorigenesis Regulates inflammation through non-hematopoietic cell compartment	[108, 109]
NLRX1	CLR 11.3; NOD5; NOD9; NOD26; DLNB26	Colorectal cancer Urethane based model of tumorigenesis Colon cancer	Regulates apoptosis in cancer cells Attenuates tumorigenesis by negative regulation of AKT and NF-κB pathways. Tumor suppression by sensitizing cells to TNF-α induced cell death via caspase-8 regulation	[175] [169] [176]
NOD1	CARD4; CLR7.1; NLRC1;	Colon-associated tumorigenesis Gastric, breast, prostate, lung and other cancer types	Maintains intestinal epithelial barrier permeability and balanced inflammatory responses Nod1 polymorphisms	[192] [193, 197]
NOD2	CARD15; CLR16.3; NLRC2	Transmissible colitis and colorectal tumorigenesis Gastric, breast, prostate, lung and other cancer types	Nod2-deficiency induces dysbiosis Nod2 mutations and polymorphisms	[194] [196, 197]
ASC	PYCARD; TMS; TMS1; CARD5	Hepatocellular carcinoma Medulloblastoma Breast cancer Ovarian cancer Colorectal cancer Glioblastoma (GBM) Melanoma	Hypermethylation of Asc gene promoter Hypermethylation of Asc highly correlated with late stage tumor Dual role in melanoma- Inhibit tumorigenesis in primary melanoma by inhibiting NF-κB and enhance NF-κB activation to induce tumorigenic pathways	[145–153, 155] [154]