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Cell Rep. 2014 Dec 11;9(5):1798-1811. doi: 10.1016/j.celrep.2014.11.016. Epub 2014 Dec 4.

Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition.

Author information

1
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.
2
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA.
3
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
4
Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
5
Department of Biology, Georgia State University, Atlanta, GA 30302, USA.
6
Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China. Electronic address: lianghoujie@sina.com.
7
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA. Electronic address: lyu123@umd.edu.

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.

PMID:
25482557
PMCID:
PMC4268306
DOI:
10.1016/j.celrep.2014.11.016
[Indexed for MEDLINE]
Free PMC Article

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