| First Author | Niu Z | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 766 |
| PubMed ID | 28974683 | Mgi Jnum | J:250127 |
| Mgi Id | MGI:6100024 | Doi | 10.1038/s41467-017-00523-6 |
| Citation | Niu Z, et al. (2017) Caspase-1 cleaves PPARgamma for potentiating the pro-tumor action of TAMs. Nat Commun 8(1):766 |
| abstractText | 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 (PPARgamma) at Asp64, thus generating a 41 kDa fragment. This truncated PPARgamma 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/PPARgamma/MCAD pathway might be a promising therapeutic approach to prevent tumor progression.Tumor associated macrophages (TAMs) promote cancer progression. Here, the author show that caspase-1 promotes TAMs differentiation by attenuating medium-chain acyl-CoA dehydrogenase activity and that inhibition of this axis results in suppression of tumour growth in a transgenic mouse model of breast cancer. |
