ALBERT

Description: Publication date: Available online 4 December 2014 Source: Cell Reports Author(s): Juanjuan Ou , Hongming Miao , Yinyan Ma , Feng Guo , Jia Deng , Xing Wei , Jie Zhou , Ganfeng Xie , Hang Shi , Bingzhong Xue , Houjie Liang , Liqing Yu 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. Graphical abstract Teaser Cancer cells shift their metabolism to aerobic glycolysis (i.e., fermentation of glucose as energy in the presence of ample oxygen), but the underlying mechanisms remain elusive. Ou et al. identify Abhd5, an activator of intracellular fat breakdown, as a suppressor of this metabolic shift and associated malignancies in colon cancer.