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

癌细胞通常会增强脂质的从头合成。然而，其功能意义仍然未知。在这项研究中，我们发现一种叫做ATP柠檬酸裂解酶（ACLY）的脂质合成酶的耗尽会阻止癌细胞的生长。这种抗癌作用在活性氧（ROS）和AMPK磷酸化水平较低的细胞中更为明显。ACLY消耗升高棕榈酸的相对丰度。由于棕榈酸可以诱导ROS，它可能有助于ACLY消耗的抗癌作用。在临床结肠肿瘤中，较高的恶性等级与较低水平的AMPK磷酸化和氧化应激相关，表明ACLY抑制可用作抗癌治疗剂。

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.