Transmembrane protein 176B promotes epithelial-mesenchymal transition in colorectal cancer through inflammasome inhibition  

作　　者：Wei Qian Chong-Yi Xu Wei Hong Zhe-Ming Li Dao-Gun Xu 

机构地区：[1]Department of Proctology,Wenling Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University,Wenling 317500,Zhejiang Province,China [2]College of Life Sciences,Zhejiang Chinese Medical University,Hangzhou 310000,Zhejiang Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2025年第3期171-187,共17页世界胃肠肿瘤学杂志(英文)

基　　金：Ministry of Education Industry-University Co-operation Collaborative Education Project,No.202102242020.

摘　　要：BACKGROUND Activation of the epithelial-mesenchymal transition(EMT),a pivotal process in tumor metastasis and evasion,as well as the NLRP3 inflammasome,both promote colorectal cancer(CRC)progression.Recent studies have shown that Transmembrane protein 176B(TMEM176B)regulates NLRP3 and promotes CRC malignant phenotypes.AIM To investigate the role of TMEM176B in modulating NLRP3 inflammasome and its implications on EMT and tumor progression in CRC.METHODS CRC in situ mouse and co-cultured cell models were established using CT26 cells,BALB/c mice,and primary cultured mouse natural killer(NK)cells.Short hairpin RNA knocked down TMEM176B and NLRP3 expression in CT26 cells.Fluorescence imaging,Terminal deoxynucleotidyl transferase dUTP nick end labeling assays,immunohistochemistry staining,flow cytometry,and molecular assays were used to investigate the effects of TMEM176B knockdown on the NLRP3 inflammasome in NK cells to assess tumor metastasis,apoptosis,and EMT indicators.RESULTS Silencing TMEM176B in CRC mice significantly reduced tumor metastasis,proliferation,and EMT,while activating apoptosis,NLRP3 inflammasome,and NK cell activity.Furthermore,silencing TMEM176B in co-cultured cell models inhibited cell migration and invasion,and promoted apoptosis.The interference of NLRP3 reversed these effects by modulating key proteins such as phosphorylated nuclear factor kappa B subunit 1 p65,matrix metallopeptidase 9,and transforming growth factor-β.CONCLUSION This study highlights the critical role of TMEM176B/NLRP3 in CRC progression and provides a basis for targeting this axis as a novel therapeutic approach to manage CRC progression and metastasis.

关 键 词：Transmembrane protein 176B Epithelial-mesenchymal transition Colorectal cancer Pyrin domain containing 3 inflammasome Natural killer cell 

分 类 号：R73[医药卫生—肿瘤]