文章：

醋酸盐在癌症中的代谢命运

The metabolic fate of acetate in cancer

原文发布日期：2016-08-26

DOI: 10.1038/nrc.2016.87

类型: Review Article

开放获取: 否

要点：

1. Acetate can be used by tumour cells as an important bioenergetic fuel or as a nutritional source to support lipid biosynthesis.
2. Acetate can be a precursor for acetylation of histones and other proteins and hence can serve as an epigenetic and post-translational modifier.
3. Despite the low circulating concentration of acetate, acetate may still exert its effects through intra- and intercellular recycling of acetate molecules within the tumour microenvironment or at sites with high local acetate concentrations.
4. Acetyl-CoA synthetase 2 (ACSS2) is emerging as an important enzyme in the growth of many different types of cancers and is induced by cancer cells in response to nutrient stress conditions. Targeting ACSS2 may prove to be a powerful therapeutic modality.
5. ACSS2 is highly upregulated in multiple cancer types and may be a useful biomarker for anti-ACSS2 therapies.
6. [¹¹C]acetate has demonstrated excellent potential as an alternative positron emission tomography imaging probe for cancer. More studies on why some but not other tumours are [¹¹C]acetate avid, and correlating these data with the expression of acetyl-CoA synthetases will aid in deciphering the exact manner by which acetate metabolism supports tumour growth and help in stratifying patients for future anti-ACSS2 therapy.

要点翻译：

1. 醋酸盐可被肿瘤细胞用作重要的生物能燃料或作为支持脂质生物合成的营养来源。
2. 醋酸盐可作为组蛋白和其他蛋白质乙酰化的前体，因此可作为表观遗传和翻译后修饰因子。
3. 尽管醋酸盐在循环中的浓度较低，但它仍可能通过肿瘤微环境内或局部醋酸盐浓度较高区域的细胞内和细胞间醋酸盐分子回收来发挥其作用。
4. 乙酰辅酶A合成酶2（ACSS2）正逐渐成为多种癌症生长中的重要酶类，并在癌细胞中因营养应激条件而被诱导产生。靶向ACSS2可能成为一种强大的治疗方式。
5. ACSS2在多种癌症类型中高度上调，可能作为抗ACSS2疗法的有用生物标志物。
6. [11C]醋酸盐已显示出作为癌症正电子发射断层扫描成像示踪剂的优异潜力。进一步研究为何部分肿瘤对[11C]醋酸盐具有高摄取性，而其他肿瘤则不然，并将这些数据与乙酰辅酶A合成酶的表达相关联，将有助于解读醋酸盐代谢支持肿瘤生长的具体机制，并为未来抗ACSS2治疗的患者分层提供依据。

英文摘要：

Recent high-profile reports have reignited an interest in acetate metabolism in cancer. Acetyl-CoA synthetases that catalyse the conversion of acetate to acetyl-CoA have now been implicated in the growth of hepatocellular carcinoma, glioblastoma, breast cancer and prostate cancer. In this Review, we discuss how acetate functions as a nutritional source for tumours and as a regulator of cancer cell stress, and how preventing its (re)capture by cancer cells may provide an opportunity for therapeutic intervention.

摘要翻译： 

近期备受关注的报告重新点燃了对癌症中乙酸代谢的兴趣。催化乙酸转化为乙酰辅酶A的乙酰辅酶A合成酶，现已被证实与肝细胞癌、胶质母细胞瘤、乳腺癌和前列腺癌的生长有关。在本综述中，我们探讨了乙酸如何作为肿瘤的营养来源以及如何调控癌细胞应激，并讨论了阻止癌细胞（重新）捕获乙酸可能为治疗干预提供机会。

原文链接：

The metabolic fate of acetate in cancer