NLRP3 通过调控上皮间质转化促进结直肠癌细胞增殖和转移。
NLRP3 Promotes Colorectal Cancer Cell Proliferation and Metastasis via Regulating Epithelial Mesenchymal Transformation.
机构信息
Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
Department of Radiology, The Qinghai Provincial People's Hospital, Xining, Qinghai, China.
出版信息
Anticancer Agents Med Chem. 2020;20(7):820-827. doi: 10.2174/1871520620666200220112741.
BACKGROUND
Nucleotide-binding domain Leucine-rich Repeat Protein 3 (NLRP3) plays a regulatory role in the immune and inflammatory responses, and has been implicated in Colorectal Cancer (CRC) progression and metastasis. However, the underlying molecular mechanisms have not been fully elucidated.
METHODS
In this study, we analyzed the expression levels of NLRP3 in human CRC tissues, and performed functional assays in CRC cell lines and a subcutaneous tumor model to elucidate its role in the development and progression of CRC.
RESULTS
In this study, we found that NLRP3 was significantly upregulated in human CRC tissues and was associated with tumor size and invasion, lymph node metastasis, venous invasion, neural invasion and TNM staging. Furthermore, knockdown of NLRP3 in CRC cells inhibited their migration and growth in vitro and in vivo, and reversed Epithelial-Mesenchymal Transition (EMT) in vitro.
CONCLUSION
Our findings indicate that NLRP3 likely regulates CRC metastasis by activating the EMT program, and is a potential therapeutic target.
背景
核苷酸结合域富含亮氨酸重复蛋白 3（NLRP3）在免疫和炎症反应中发挥调节作用，并与结直肠癌（CRC）的进展和转移有关。然而，其潜在的分子机制尚未完全阐明。
方法
本研究分析了 NLRP3 在人 CRC 组织中的表达水平，并在 CRC 细胞系和皮下肿瘤模型中进行了功能测定，以阐明其在 CRC 发生和发展中的作用。
结果
本研究发现，NLRP3 在人 CRC 组织中显著上调，与肿瘤大小和侵袭、淋巴结转移、静脉侵犯、神经侵犯和 TNM 分期有关。此外，CRC 细胞中 NLRP3 的敲低抑制了其在体外和体内的迁移和生长，并逆转了体外的上皮-间充质转化（EMT）。
结论
我们的研究结果表明，NLRP3 可能通过激活 EMT 程序来调节 CRC 的转移，是一个潜在的治疗靶点。
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