Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM.
Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM.
复制标题
巨噬细胞 ABHD5 通过 SRM 抑制亚精胺的产生来促进结直肠癌的生长。
DOI：
10.1038/ncomms11716
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发表时间：
2016-05-18
影响因子：
16.6
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Miao H;Ou J;Peng Y;Zhang X;Chen Y;Hao L;Xie G;Wang Z;Pang X;Ruan Z;Li J;Yu L;Xue B;Shi H;Shi C;Liang H
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/EBPɛ, 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. ABHD5 is a co-activator of lipolysis. Here the authors show that in tumour-associated macrophages ABHD5 inhibits ROS-dependent induction of C/EBPɛ, which transcriptionally activates spermidine synthase, and that blocking ABHD5 delays colorectal cancer growth in mice by inhibiting spermidine production.
