| First Author | Miao H | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11716 | PubMed ID | 27189574 |
| Mgi Jnum | J:239925 | Mgi Id | MGI:5882029 |
| Doi | 10.1038/ncomms11716 | Citation | Miao H, et al. (2016) Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM. Nat Commun 7:11716 |
| abstractText | Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM-derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPvarepsilon, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene-induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy. |
