NLRP1 inhibits lung adenocarcinoma growth through mediating mitochondrial dysregulation in an inflammasome-independent manner
| Autor: | Chen-jing Lin, Guang-ang Tian, Wen-ya Zhao, Yi Tian, Yi-ru Liu, Dian-na Gu, Ling Tian |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Brazilian Journal of Medical and Biological Research, Vol 57 (2024) |
| Druh dokumentu: | article |
| ISSN: | 1414-431X 1414-431x |
| DOI: | 10.1590/1414-431x2024e13885 |
| Popis: | NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment. |
| Databáze: | Directory of Open Access Journals |
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