Caspase-1 cleaves PPAR gamma for potentiating the pro-tumor action of   TAMs

doi:10.1038/s41467-017-00523-6

CORC > 北京大学 > 生命科学学院

	Caspase-1 cleaves PPAR gamma for potentiating the pro-tumor action of TAMs
	Niu, Zhiyuan ; Shi, Qian ; Zhang, Wenlong ; Shu, Yuxin ; Yang, Nanfei ; Chen, Bing ; Wang, Qingsong ; Zhao, Xuyang ; Chen, Jiajia ; Cheng, Nan ; Feng, Xiujing ; Hua, Zichun ; Ji, Jianguo ; Shen, Pingping
刊名	NATURE COMMUNICATIONS
	2017
关键词	BREAST-CANCER METASTASIS MACROPHAGE POLARIZATION CONVERTING-ENZYME LIPID-METABOLISM RECEPTOR CELLS ANGIOGENESIS ACCUMULATION INFLAMMATION ADIPOCYTES
DOI	10.1038/s41467-017-00523-6
英文摘要	Tumor-associated macrophages are increasingly viewed as a target of great relevance in the tumor microenvironment, because of their important role in cancer progression and metastasis. However, the endogenous regulatory mechanisms underlying tumor-associated macrophage differentiation remain largely unknown. Here, we report that caspase-1 promotes tumor-associated macrophage differentiation by cleaving peroxisome proliferator-activated receptor gamma (PPAR gamma) at Asp64, thus generating a 41 kDa fragment. This truncated PPAR gamma translocates to mitochondria, where it directly interacts with medium-chain acyl-CoA dehydrogenase (MCAD). This binding event attenuates MCAD activity and inhibits fatty acid oxidation, thereby leading to the accumulation of lipid droplets and promoting tumor-associated macrophage differentiation. Furthermore, the administration of caspase-1 inhibitors or the infusion of bone marrow-derived macrophages genetically engineered to overexpress murine MCAD markedly suppresses tumor growth. Therefore, targeting the caspase-1/PPAR gamma/MCAD pathway might be a promising therapeutic approach to prevent tumor progression.; National Natural Science Foundation of China [81273527, 81421091, 81473220, 81673439, 91013015]; National Key Research and Development Program of China [2017YFA0205400]; JDRF advanced postdoc fellowship award, USA [3-APF-2016-205-A-N]; SCI(E); ARTICLE; 8
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/470517]
专题	生命科学学院
推荐引用方式 GB/T 7714	Niu, Zhiyuan,Shi, Qian,Zhang, Wenlong,et al. Caspase-1 cleaves PPAR gamma for potentiating the pro-tumor action of TAMs[J]. NATURE COMMUNICATIONS,2017.
APA	Niu, Zhiyuan.,Shi, Qian.,Zhang, Wenlong.,Shu, Yuxin.,Yang, Nanfei.,...&Shen, Pingping.(2017).Caspase-1 cleaves PPAR gamma for potentiating the pro-tumor action of TAMs.NATURE COMMUNICATIONS.
MLA	Niu, Zhiyuan,et al."Caspase-1 cleaves PPAR gamma for potentiating the pro-tumor action of TAMs".NATURE COMMUNICATIONS (2017).