title: Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition.
abstract: How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of α/β-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in Apc(Min/+) mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKα-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressing Abhd5-mediated intracellular lipolysis.
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Ou
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Bingzhong
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China. Electronic address: lianghoujie@sina.com.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA. Electronic address: lyu123@umd.edu.
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D000332:Aerobiosis; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006019:Glycolysis; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C439972:ABHD5 protein, human