Background
Classification of pattern recognition receptors (PRRs)
Structure of the NLR family
Inflammasome history
Inflammasome oligomerization
The NLRP3 inflammasome complex
NLRP3 inflammasome complex activation
Role of the NLRP3 inflammasome in cancer
Type of cancer | Source of experimental evidence | Outcome | Suggested mechanism | References |
---|---|---|---|---|
HNSCC | - HNSCC cell lines (A253) -Oral cancer tissue | Activation of NLRP3 inflmmasome closely associated with survival and invasiveness of HNSCC | Activation of IL-1β | [99] |
-HNSCC tissue - HNSCC cell lines(CAL27, SCC9, SCC25, and FaDu) - transgenic mouse HNSCC model | NLRP3 inflammasome related with the tumorgenesis and CSCs markers self-renewal activation | -overexpression of CSCs markers (BMI1, ALDH1 and CD44) | [100] | |
GBM | -U87 and GL261 xenograft mouse GBM model | NLRP3 inflammasome involved in resistance to radiotherapy | -regulation of numerous aging-related genes in hippocampus | [150] |
OSCC | - OSC cells lines (WS UHN6 and C AL27) -NLRP3−/− and Caspase1−/− mice -OSCC tissue | NLRP3 inflammasome increased resistance of OSCC to 5-FU | Promotion of the IL-1β production | [106] |
BC | - BC cell lines(LLC and E0771) -C57BL/6 mice | tumor-infiltrating regulation of NLRP3 strongly linked with tumor invasiveness, migration and outcome | IL-1β secretion and S1PR1 signaling | [123] |
GC | -GC tissue -GC cell lines (SGC-7901, BGC-823, HGC-27 and AGS) -normal gastric epithelial cell line (GES-1) | NLRP3 inflammasome stimulates epithelial cells proliferation and GC carcinogenesis | -IL-1 β secretion -enhance cyclin-D1 transcription | [77] |
CAC | -NLRP3−/−, Pycard−/− and Caspase1−/− mice | Mice with inflammasome compartment deficiency were extremely susceptible to AOM/DSS- induced colitis | -reduction in IL-18 | [67] |
-NLRP3−/− mouse | NLRP3−/− mouse is more susceptible to acute and recurrence CAC | -increasing pro–IL-1β and IL-18 secretion | [85] | |
-NLRP3−/− and Caspase1−/− mice | NLRP3−/− and Caspase1−/− mice were more susceptible to AOM/DSS-induced inflammation and increased tumor burdens | - NLRP3 inflammasome deficiency lead to reduction in secretion and activation of the tumor IFN-γ and STAT1 | [86] | |
-NLRP3−/−, ASC−/−, Caspase1−/−, cathepsin B−/− or cathepsin L−/−mice- | NLRP deficient mice were significantly protected from colitis | IL-1β secretion was abrogated in macrophages without NLRP3, ASC or Caspase-1 | [165] | |
CRC | -CRC and adjacent normal tissue | NLRP3 gene variation are correlated with worse survival | -elevatating IL-1β and IL-6 levels | [89] |
CRC metastatic in liver | -Inflammasome components −/− mouse | NLRP3 inflammasome inhibits liver CRC metastatic growth | -enhancing NK cell tumoricidal action | [91] |
Fibrosarcoma | -NLRP3−/− mouse model | NLRP3-deficient mice were less resistant to tumor formation | -NLRP3 suppressed NK cell | [116] |
Melanoma | -Human melanoma cell lines (A375) -mouse melanoma cell lines (B16F10) | Inhibition of NLRP3 inflmmasome blocked melanoma migration | -inhibition of NLRP3 inflmmasome suppressed secretion of cytokines IL-1β and IL-18 | [139] |
Cervical Cancer | -HPV+ and adjacent normal tissue | NLRP3 polymorphism related with a lower risk of HPV infection | -innate immune anti-viral response - obliteration of virus persistence and viral elimination | [144] |
Lung cancer | -human alveolar epithelial adenocarcinoma cell line (A549) | NLRP3 inflmmasome regulate the proliferation and metastasis of lung cancer | -promoting phosphorylation of Akt, ERK1/2, and CREB -enhancing the expression of Snail -decrement of E-cadherin expression | [112] |
HCC | -HCC tissues and adjacent normal tissues | -Down regulation of all of the NLRP3 inflammasome elements associated with HCC occurrence, advanced tumor stages and poor differentiation | NR | [96] |