炎症体
STAT1
癌症研究
信号转导
热带假丝酵母
基因敲除
化学
癌变
细胞生物学
生物
炎症
免疫学
细胞凋亡
生物化学
基因
酵母
作者
Zhiyong Zhang,Ying Chen,Yuxin Yin,Yuxi Chen,Qianyu Chen,Ziqian Bing,Yaojun Zheng,Yayi Hou,Shihao Shen,Yitian Chen,Tingting Wang
标识
DOI:10.1016/j.intimp.2022.109430
摘要
Our previous studies showed that Candida tropicalis promoted colorectal cancer (CRC) by activating the function of MDSCs. However, underlying molecular mechanisms remains to be further investigated. In the present study, we indicated that C. tropicalis induced NLRP3 inflammasome activation through Dectin-3 in myeloid-derived suppressor cells (MDSCs). Mechanistically, we identified that C. tropicalis significantly enhanced the levels of glycolysis dependent on glycogen metabolism in MDSCs, which was required for NLRP3 inflammasome activation. C. tropicalis-induced NLRP3 inflammasome activation of MDSCs required the first priming signal and the second activation signal. For one thing, C. tropicalis promoted transcription of Nlrp3, Pro-caspase-1 and IL-1β genes through activation of JAK-STAT1 signaling pathway. For another, mtROS as the second activation signal mediated C. tropicalis-induced activation of NLRP3 inflammasome. Pharmacological inhibition of NLRP3 inflammasome activation abolished the pro-tumorigenic effect of C. tropicalis in an AOM/DSS-induced CAC mice model and significantly reduced C. tropicalis-promoted infiltration of MDSCs in colon tumors. Finally, in human CRC samples, the expression of STAT1, p-STAT1 and NLRP3 was elevated in MDSCs infiltrated by CRC. Collectively, these findings shed light on a previously unidentified mechanism by which C. tropicalis induces NLRP3 inflammasome activation in MDSCs to contribute to the progression of CRC. And STAT1-NLRP3 axis might represent a prospective therapeutic target for the treatment of CRC.
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