Peroxiredoxin 6 triggers melanoma cell growth by increasing arachidonic acid-dependent lipid signalling
Peroxiredoxin 6 triggers melanoma cell growth by increasing arachidonic acid-dependent lipid signalling
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DOI：
10.1042/bj20141204
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发表时间：
2015-10-15
影响因子：
4.1
通讯作者：
Meierjohann, Svenja
中科院分区：
文献类型：
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作者：
Schmitt, Alexandra;Schmitz, Werner;Meierjohann, Svenja
据报道，肿瘤细胞表现出ROS（活性氧）水平的不平衡。通常情况下，ROS产生的增加沿着抗氧化酶的补偿性上调。因此，我们在先前的研究中发现，在实验诱导的黑色素瘤中，包括PRDX6（peroxiredoxin 6）在内的几种过氧化物酶的蛋白质水平高度升高。在本研究中，我们研究了PRDX6在人黑色素瘤细胞中的功能作用。PRDX6是一种双功能酶，除了其过氧化物酶功能外，还具有iPLA 2（Ca2+非依赖性磷脂酶A2）活性。我们的研究结果表明，PRDX6是强烈表达在大多数黑色素瘤细胞和其表达水平维持在转录后的方式，特别是通过EGFR（表皮生长因子受体）依赖性信号。PRDX6主要通过增强增殖来增强细胞活力，这沿着Src家族激酶的活化。有趣的是，我们能够证明该酶的磷脂酶活性介导PRDX6的促增殖作用。我们确定AA（花生四烯酸）作为PRDX6依赖性增殖和Src家族激酶激活诱导剂的关键效应子。这些结果进一步支持了黑色素瘤中脂质信号传导的新兴领域的生物学重要性，并突出了PRDX6依赖性磷脂酶活性的特定功能相关性。
Tumour cells are reported to display an imbalance in the levels of ROS (reactive oxygen species). Frequently, elevated ROS production goes along with compensatory up-regulation of antioxidant enzymes. Accordingly, we found in a previous study that protein levels of several peroxiredoxins, including PRDX6 (peroxiredoxin 6), are highly elevated in experimentally induced melanomas. In the present study, we investigated the functional role of PRDX6 in human melanoma cells. PRDX6 is a bifunctional enzyme, which harbours iPLA2 (Ca2+-independent phospholipase A2) activity in addition to its peroxidase function. Our results show that PRDX6 is strongly expressed in most melanoma cells and its expression levels are maintained in a post-transcriptional manner, particularly by EGFR (epidermal growth factor receptor)-dependent signalling. PRDX6 enhances cell viability mainly by enhancing proliferation, which goes along with activation of Src family kinases. Interestingly, we were able to show that the phospholipase activity of the enzyme mediates the pro-proliferative effect of PRDX6. We identified AA (arachidonic acid) as a crucial effector of PRDX6-dependent proliferation and inducer of Src family kinase activation. These results support further the biological importance of the emerging field of lipid signalling in melanoma and highlight the particular functional relevance of PRDX6-dependent phospholipase activity.