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Ether lipid and sphingolipid expression patterns are estrogen receptor-dependently altered in breast cancer cells.
The International Journal of Biochemistry & Cell Biology ( IF 3.4 ) Pub Date : 2020-08-19 , DOI: 10.1016/j.biocel.2020.105834
Lisa Hahnefeld 1 , Lisa Gruber 1 , Nina Schömel 1 , Caroline Fischer 1 , Peter Mattjus 2 , Robert Gurke 3 , Martina Beretta 4 , Nerea Ferreirós 1 , Gerd Geisslinger 3 , Marthe-Susanna Wegner 5
Affiliation  

Identifying co-expression of lipid species is challenging, but indispensable to identify novel therapeutic targets for breast cancer treatment. Lipid metabolism is often dysregulated in cancer cells, and changes in lipid metabolism affect cellular processes such as proliferation, autophagy, and tumor development. In addition to mRNA analysis of sphingolipid metabolizing enzymes, we performed liquid chromatography time-of-flight mass spectrometry analysis in three breast cancer cell lines. These breast cancer cell lines differ in estrogen receptor and G-protein coupled estrogen receptor 1 status. Our data show that sphingolipids and non-sphingolipids are strongly increased in SKBr3 cells. SKBr3 cells are estrogen receptor negative and G-protein coupled estrogen receptor 1 positive. Treatment with G15, a G-protein coupled estrogen receptor 1 antagonist, abolishes the effect of increased sphingolipid and non-sphingolipid levels in SKBr3 cells. In particular, ether lipids are expressed at much higher levels in cancer compared to normal cells and are strongly increased in SKBr3 cells. Our analysis reveals that this is accompanied by increased sphingolipid levels such as ceramide, sphingadiene-ceramide and sphingomyelin. This shows the importance of focusing on more than one lipid class when investigating molecular mechanisms in breast cancer cells. Our analysis allows unbiased screening for different lipid classes leading to identification of co-expression patterns of lipids in the context of breast cancer. Co-expression of different lipid classes could influence tumorigenic potential of breast cancer cells. Identification of co-regulated lipid species is important to achieve improved breast cancer treatment outcome.



中文翻译:

乙醚脂质和鞘脂的表达模式在乳腺癌细胞中是雌激素受体依赖性改变的。

确定脂质种类的共表达具有挑战性,但对于确定乳腺癌治疗的新治疗靶点是必不可少的。癌细胞中的脂质代谢经常失调,脂质代谢的变化会影响细胞过程,如增殖、自噬和肿瘤发展。除了鞘脂代谢酶的 mRNA 分析外,我们还对三种乳腺癌细胞系进行了液相色谱飞行时间质谱分析。这些乳腺癌细胞系在雌激素受体和 G 蛋白偶联雌激素受体 1 状态方面存在差异。我们的数据显示鞘脂和非鞘脂在 SKBr3 细胞中强烈增加。SKBr3 细胞雌激素受体阴性,G 蛋白偶联雌激素受体 1 阳性。用 G15 处理,一种 G 蛋白偶联雌激素受体 1 拮抗剂,可消除 SKBr3 细胞中增加的鞘脂和非鞘脂水平的影响。特别是,与正常细胞相比,醚脂质在癌症中的表达水平要高得多,并且在 SKBr3 细胞中的表达水平显着增加。我们的分析表明,这伴随着鞘脂水平的增加,如神经酰胺、鞘氨醇-神经酰胺和鞘磷脂。这表明在研究乳腺癌细胞的分子机制时关注不止一种脂质类的重要性。我们的分析允许对不同的脂质类别进行无偏见的筛选,从而确定乳腺癌背景下脂质的共表达模式。不同脂质类别的共表达可能影响乳腺癌细胞的致瘤潜力。

更新日期:2020-08-19
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