Manganese superoxide dismutase promotes interaction of actin, S100A4 and Talin, and enhances rat gastric tumor cell invasion.
Manganese superoxide dismutase promotes interaction of actin, S100A4 and Talin, and enhances rat gastric tumor cell invasion.
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DOI：
10.3164/jcbn.14-146
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发表时间：
2015-07
影响因子：
2.4
通讯作者：
Majima HJ
中科院分区：
文献类型：
--
作者：
Indo HP;Matsui H;Chen J;Zhu H;Hawkins CL;Davies MJ;Yarana C;St Clair DK;Majima HJ
已证明，癌细胞处于高水平的氧化应激下，并表达高水平的锰超氧化物歧化酶 (MnSOD)，以保护自身并支持生长和细胞运动所需的合成代谢。本研究的目的是鉴定可能与线粒体活性氧 (ROS) 的入侵和氧化还原调节相关的蛋白质。 MnSOD 清除线粒体产生的超氧阴离子，是细胞氧化还原状态的重要调节剂。半胱氨酸残基的氧化翻译后修饰是调节蛋白质结构和功能的关键机制。我们假设 MnSOD 调节细胞内还原硫醇状态并促进癌症侵袭。使用 5-碘乙酰胺荧光素的蛋白质组硫醇标记方法用于鉴定细胞内含还原硫醇蛋白质的变化。我们的结果表明，MnSOD 的过度表达使主要结构蛋白肌动蛋白维持在还原状态，并增强了胃粘膜癌细胞 RGK1 的侵袭能力。我们还发现在MnSOD过表达的RGK1细胞中Talin和S100A4的表达增加。此外，Talin 不仅与肌动蛋白结合，还与 S100A4 结合，表明这些蛋白质的相互作用可能在一定程度上有助于大鼠胃癌的侵袭能力。
It has been demonstrated that cancer cells are under high levels of oxidative stress and express high levels of Manganese superoxide dismutase (MnSOD) to protect themselves and support the anabolic metabolism needed for growth and cell motility. The aim of this study was to identify proteins that may have a correlation with invasion and redox regulation by mitochondrial reactive oxygen species (ROS). MnSOD scavenges superoxide anions generated from mitochondria and is an important regulator of cellular redox status. Oxidative posttranslational modification of cysteine residues is a key mechanism that regulates protein structure and function. We hypothesized that MnSOD regulates intracellular reduced thiol status and promotes cancer invasion. A proteomic thiol-labeling approach with 5-iodoacetamidofluorescein was used to identify changes in intracellular reduced thiol-containing proteins. Our results demonstrate that overexpression of MnSOD maintained the major structural protein, actin, in a reduced state, and enhanced the invasion ability in gastric mucosal cancer cells, RGK1. We also found that the expression of Talin and S100A4 were increased in MnSOD-overexpressed RGK1 cells. Moreover, Talin bound not only with actin but also with S100A4, suggesting that the interaction of these proteins may, in part, contribute to the invasive ability of rat gastric cancer.