| Title | Caspase-1 cleaves PPAR gamma for potentiating the pro-tumor action of TAMs |
| Authors | 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 |
| Affiliation | Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Model Anim Res Ctr, Nanjing 210023, Jiangsu, Peoples R China. Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210023, Jiangsu, Peoples R China. Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Integrat Physiol, STRF Greehey North Campus,8403 Floyd Curl Dr, San Antonio, TX 78229 USA. Nanjing Univ, Affiliated Hosp, Nanjing Drum Tower Hosp, Dept Hematol,Med Sch, Nanjing 210008, Jiangsu, Peoples R China. Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Sch Life Sci, Nanjing 210023, Jiangsu, Peoples R China. Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Model Anim Res Ctr, Nanjing 210023, Jiangsu, Peoples R China. Shen, PP (reprint author), Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210023, Jiangsu, Peoples R China. |
| Keywords | BREAST-CANCER METASTASIS MACROPHAGE POLARIZATION CONVERTING-ENZYME LIPID-METABOLISM RECEPTOR CELLS ANGIOGENESIS ACCUMULATION INFLAMMATION ADIPOCYTES |
| Issue Date | 2017 |
| Publisher | NATURE COMMUNICATIONS |
| Citation | NATURE COMMUNICATIONS.2017,8. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/470517 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-017-00523-6 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 |
