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Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM.


ABSTRACT: 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/EBP?, 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.

SUBMITTER: Miao H 

PROVIDER: S-EPMC4873969 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM.

Miao Hongming H   Ou Juanjuan J   Peng Yuan Y   Zhang Xuan X   Chen Yujuan Y   Hao Lijun L   Xie Ganfeng G   Wang Zhe Z   Pang Xueli X   Ruan Zhihua Z   Li Jianjun J   Yu Liqing L   Xue Bingzhong B   Shi Hang H   Shi Chunmeng C   Liang Houjie H  

Nature communications 20160518


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  ...[more]

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