Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Braz J Med Biol Res. 2024 Sep 6;57:e13885. doi: 10.1590/1414-431X2024e13885. eCollection 2024.
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.
NLRP1 是第一个被鉴定的炎症小体形成传感器，被认为与癌症有关，但它在肺腺癌 (LUAD) 中的明确功能仍不清楚。在此，我们研究了 NLRP1 在 LUAD 中的表达和功能。发现 NLRP1 在 LUAD 中的表达降低，与预后不良相关。NLRP1 的过表达在体外和体内均抑制肿瘤生长。从机制上看，这种作用与炎症小体的激活无关。进一步的研究表明，NLRP1 的过表达下调了 DRP1 的磷酸化水平，促进了线粒体融合，这是通过抑制 NF-κB 活性介导的。NF-κB 激动剂可以中和 NLRP1 对线粒体动力学的影响。此外，由于上调的 NLRP1 导致线粒体分裂减少，LUAD 对顺铂的敏感性增强。总之，我们的研究结果表明 NLRP1 通过调节线粒体活性在 LUAD 中发挥了意想不到的作用，为其在 LUAD 治疗中的应用提供了有力证据。
