Lipid metabolomics to analyze the mechanisms for cellular adaptation to tumor microenvironment

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Cancer cells often enhance de novo lipid synthesis. However, its functional significance remains unknown. In this study, we found that depletion of a lipid-synthesizing enzyme, called ATP citrate lyase(ACLY), blocks cancer cell growth. This anticancer effect was more evident in those cells with lower reactive oxygen species(ROS) and lower phosphorylation level of AMPK. ACLY depletion elevated the relative abundance of palmitate. Because palmitate can induce ROS, it may contribute to the anticancer effect of ACLY depletion. In clinical colon tumors, higher malignant grades correlated with lower levels of AMPK phosphorylation and oxidative stress, suggesting that ACLY inhibition can be utilized as an anticancer therapeutics.