Copper chaperone Atox1 plays role in breast cancer cell migration

Copper chaperone Atox1 plays role in breast cancer cell migration
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DOI:
10.1016/j.bbrc.2016.12.148
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发表时间:
2017-01-29
影响因子:
3.1
通讯作者:
Wittung-Stafshede, Pernilla
Wittung-Stafshede, Pernilla
中科院分区:
生物学4区
文献类型:
--
作者:
Blockhuys, Stephanie;Wittung-Stafshede, Pernilla

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铜(Cu)是一种重要的过渡金属离子,在许多关键酶中作为辅因子被需要.细胞摄取铜后,金属被细胞质铜分子伴侣Atox1转运到高尔基体网络中的P1B型ATP酶,以并入分泌途径中的铜依赖性酶中。铜对癌症进展的许多步骤至关重要,Atox1最近被认为具有作为核转录因子的额外功能。我们在这里调查的表达水平,细胞定位和Atox1在细胞迁移中的作用,在结合免疫染色,显微镜和伤口愈合试验的侵袭性乳腺癌细胞系。我们意外地发现Atox1在迁移的癌细胞的板状伪足边界处积累,并且Atox1沉默导致迁移缺陷,如伤口闭合减少所证明的。因此,我们发现了一个未知的作用,铜伴侣Atox1在乳腺癌细胞迁移。(C)2016作者爱思唯尔公司出版
Copper (Cu) is an essential transition metal ion required as cofactor in many key enzymes. After cell uptake of Cu, the metal is transported by the cytoplasmic Cu chaperone Atox1 to P1B-type ATPases in the Golgi network for incorporation into Cu-dependent enzymes in the secretory path. Cu is vital for many steps of cancer progression and Atox1 was recently suggested to have additional functionality as a nuclear transcription factor. We here investigated the expression level, cellular localization and role in cell migration of Atox1 in an aggressive breast cancer cell line upon combining immunostaining, microscopy and a wound healing assay. We made the unexpected discovery that Atox1 accumulates at lamellipodia borders of migrating cancer cells and Atox1 silencing resulted in migration defects as evidenced from reduced wound closure. Therefore, we have discovered an unknown role of the Cu chaperone Atox1 in breast cancer cell migration. (C) 2016 The Authors. Published by Elsevier Inc.