Mitochondrial Ca2+ uniporter is critical for store-operated Ca2+ entry-dependent breast cancer cell migration

Mitochondrial Ca2+ uniporter is critical for store-operated Ca2+ entry-dependent breast cancer cell migration
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线粒体 Ca2 单向转运蛋白对于库操作的 Ca2 进入依赖性乳腺癌细胞迁移至关重要

DOI:
10.1016/j.bbrc.2015.01.092
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发表时间:
2015-02-27
影响因子:
3.1
通讯作者:
Zou, Fei
Zou, Fei
中科院分区:
生物学4区
文献类型:
--
作者:
Tang, Shihao;Wang, Xubu;Zou, Fei

文献摘要

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癌细胞的转移是一个复杂的多步骤过程,需要广泛和连续的胞浆钙调节。线粒体Ca 2+单向转运体(MW)是线粒体Ca 2+摄取的调节因子,参与能量代谢和多种细胞信号转导过程。然而,MCU是否有助于癌细胞迁移尚未确定。在这里,我们检查了Oncomine数据库中MCU mRNA的表达,发现MW与转移和浸润性乳腺癌相关。通过钌红(RuR)抑制MCU或通过siRNA沉默MCU可消除血清诱导的MDA-MB-231乳腺癌细胞迁移,并减少血清或毒胡萝卜素(TG)诱导的钙库操纵的钙内流(SOCE)。血清诱导的MDA-MB-231细胞迁移被SOCE抑制剂阻断。我们的研究结果表明,MCU通过调节SOCE在乳腺癌细胞迁移中起着关键作用。(C)2015 Elsevier Inc. All rights reserved.
Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca2+ uniporter (MW), a regulator of mitochondrial Ca2+ uptake, has been implicated in energy metabolism and various cellular signaling processes. However, whether MCU contributes to cancer cell migration has not been established. Here we examined the expression of MCU mRNA in the Oncomine database and found that MW is correlated to metastasis and invasive breast cancer. MCU inhibition by ruthenium red (RuR) or MCU silencing by siRNA abolished serumi-nduced migration in MDA-MB-231 breast cancer cells and reduced serum- or thapsigargin (TG)induced store-operated Ca2+ entry (SOCE). Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. Our results demonstrate that MCU plays a critical role in breast cancer cell migration by regulating SOCE. (C) 2015 Elsevier Inc. All rights reserved.