title: 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/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.
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Ou
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.
authors.forename: Bingzhong
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Oncology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D000818:Animals; D015179:Colorectal Neoplasms / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000067996:RAW 264.7 Cells; D013095:Spermidine / Q000096:biosynthesis*; D011436:Spermidine Synthase / Q000378:metabolism*
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C492986:Abhd5 protein, mouse; D011436:Spermidine Synthase; D013095:Spermidine