NLRP3 Promotes Colorectal Cancer Cell Proliferation and Metastasis via Regulating Epithelial Mesenchymal Transformation

• Published in: Anti-cancer agents in medicinal chemistry Vol. 20; no. 7; p. 820
• Main Authors: Shao, Xinyu, Lei, Zhiyi, Zhou, Chunli
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2020
• Subjects: Animals; Cell Movement; Cell Proliferation; Cell Survival; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Epithelial-Mesenchymal Transition; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Retrospective Studies; Tumor Cells, Cultured; NLRP3; TNM; epithelial-mesenchymal transition; therapeutic target; metastasis; Colorectal cancer
• ISSN: 1875-5992
• DOI: 10.2174/1871520620666200220112741

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. 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. 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. Our findings indicate that NLRP3 likely regulates CRC metastasis by activating the EMT program, and is a potential therapeutic target.