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Nat Commun. 2016 May 18;7:11716. doi: 10.1038/ncomms11716.

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

Author information

1
Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
2
Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland 20742, USA.
3
Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.
4
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.

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/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.

PMID:
27189574
PMCID:
PMC4873969
DOI:
10.1038/ncomms11716
[Indexed for MEDLINE]
Free PMC Article

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