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Nature:线粒体蛋白调节脂代谢抑制乳腺癌细胞增殖

2017-03-23 Leo.C MedSci原创

线粒体蛋白调节脂代谢抑制乳腺癌细胞增殖

不同于恶性生长的新生肿瘤细胞,正常细胞在减数分裂之后开始展现出抑制细胞生长的特性,其中包括表达一系列抑制细胞周期的蛋白。因此比较这些已经分化后的细胞也许能找到新的一些抑制细胞生长的基因,从而有可能成为抑制肿瘤细胞生长的关键因素。

在最新上线的Nature杂志中,Zuzana Keckesova及其同事,发现线粒体蛋白LACTB能够通过调节细胞的脂代谢从而抑制乳腺癌细胞的增殖。

乳腺,肺和大肠这些器官组织产生癌细胞的几率要大于心脏,肌肉和大脑。这种现象暗示了分化成心脏,肌肉和大脑中的细胞可能有特定的基因特征,使他们不容易癌变从而恶性生长。本文的研究组通过比较实验小鼠和人的肌肉细胞与各种癌细胞发现一种LACTB的基因在癌细胞中的表达量特定下调,但是在其他正常细胞,如肌肉,心脏和肝中普遍表达。

通过体外实验和癌细胞移植实验发现,在癌细胞内诱导表达LACTB蛋白能够抑制乳腺癌细胞的增殖与分化。因为LACTB是一种线粒体的内网蛋白,研究组试图阐述是否LACTB通过调节线粒体的功能从而抑制癌细胞的增殖。研究者发现,在乳腺癌细胞增殖分化的前24小时内,表达LACTB并没有造成任何的包括ATP和氧化自由基(ROS)的产量的不同,线粒体膜功能的不同或者线粒体数量及结构的不同。然而,当癌细胞分化到后期(3-6天),LACTB的表达导致上述的线粒体的功能产生明显不同。通过质谱分析诱导表达LACTB后的癌细胞发现,溶血磷脂酰乙醇胺(lysophosphatidylethanolamines, LPE)以及磷酯酰乙醇胺(phosphatidylethanolamines,PE)的产生在诱导LACTB的表达的24小时内大幅下降。研究人员在培养癌细胞的培养基中加入了溶血磷脂酰乙醇胺发现其能促进癌细胞的增殖和分化。从而表明诱导表达LACTB蛋白是通过抑制癌细胞的溶血磷脂酰乙醇胺从而抑制癌细胞的增殖与分化。

这项研究发现了一个具有抑制癌细胞增长功能的新的线粒体蛋白,也将线粒体的脂代谢功能和乳腺癌细胞的生长和增殖联系起来。

原始出处:
Zuzana Keckesova, Joana Liu Donaher, Jasmine De Cock et al., LACTB is a tumour suppressor that modulates lipid metabolism and cell state. Nature (2017) doi:10.1038/nature21408

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    2017-12-01 liye789132251
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    2017-03-25 yxch36
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    2017-03-25 huangdf

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目前,关于高血压与乳腺癌风险之间相关性的研究存在一定的矛盾。近期,一项发表在杂志Sci Rep上的研究进行了系统评价和荟萃分析,总结了有关高血压与乳腺癌风险之间的相关证据。通过对PubMed、EMBASE和Cochrane图书馆的综合文献检索,确定截至2016年8月的相关合格研究。此项荟萃分析包括报告了相对风险(RR)与相应95%置信区间(CI)的观察性研究。通过使用随机效应模型汇集个人研究结果。

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