Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2.
Exp Cell Res. 2014 Jan 15;320(2):302-10. doi: 10.1016/j.yexcr.2013.10.016. Epub 2013 Nov 4.
Fatty acid synthase is over-expressed in many cancers and its activity is required for cancer cell survival, but the role of endogenously synthesized fatty acids in cancer is unknown. It has been suggested that endogenous fatty acid synthesis is either needed to support the growth of rapidly dividing cells, or to maintain elevated glycolysis (the Warburg effect) that is characteristic of cancer cells. Here, we investigate both hypotheses. First, we compared utilization of fatty acids synthesized endogenously from (14)C-labeled acetate to those supplied exogenously as (14)C-labeled palmitate in the culture medium in human breast cancer (MCF-7 and MDA-MB-231) and untransformed breast epithelial cells (MCF-10A). We found that cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, that these fatty acids are esterified to the same lipid and phospholipid classes in the same proportions, and that their distribution within neutral lipids is not different from untransformed cells. These results suggest that endogenously synthesized fatty acids do not fulfill a specific function in cancer cells. Furthermore, we observed that cancer cells excrete endogenously synthesized fatty acids, suggesting that they are produced in excess of requirements. We next investigated whether lipogenic activity is involved in the maintenance of high glycolytic activity by culturing both cancer and non-transformed cells under anoxic conditions. Although anoxia increased glycolysis 2-3 fold, we observed no concomitant increase in lipogenesis. Our results indicate that breast cancer cells do not have a specific qualitative or quantitative requirement for endogenously synthesized fatty acids and that increased de novo lipogenesis is not required to sustain elevations in glycolytic activity induced by anoxia in these cells.
脂肪酸合酶在许多癌症中过度表达，其活性是癌细胞存活所必需的，但内源性合成的脂肪酸在癌症中的作用尚不清楚。有人认为，内源性脂肪酸的合成要么是为了支持快速分裂细胞的生长，要么是为了维持癌细胞特有的糖酵解（Warburg 效应）升高。在这里，我们研究了这两种假说。首先，我们比较了人乳腺癌（MCF-7 和 MDA-MB-231）和未转化的乳腺上皮细胞（MCF-10A）中从（14）C 标记的醋酸盐内源性合成的脂肪酸与培养基中外源提供的（14）C 标记的棕榈酸的利用情况。我们发现，癌细胞所产生的脂肪酸与外源性棕榈酸衍生的脂肪酸没有不同，这些脂肪酸被酯化到相同的脂质和磷脂类中，并且它们在中性脂质中的分布与未转化的细胞没有不同。这些结果表明，内源性合成的脂肪酸在癌细胞中没有发挥特定的功能。此外，我们观察到癌细胞分泌内源性合成的脂肪酸，表明它们的产生超过了需要。接下来，我们研究了在缺氧条件下培养癌细胞和非转化细胞时，脂肪生成活性是否参与维持高糖酵解活性。尽管缺氧使糖酵解增加了 2-3 倍，但我们没有观察到脂肪生成相应增加。我们的结果表明，乳腺癌细胞对内源性合成的脂肪酸没有特定的定性或定量需求，并且增加从头脂肪生成并不需要维持这些细胞中缺氧诱导的糖酵解活性升高。
