当前位置: X-MOL 学术Proc. Natl. Acad. Sci. U.S.A. › 论文详情
Single-cell tracking demonstrates copper chaperone Atox1 to be required for breast cancer cell migration.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2020-01-13 , DOI: 10.1073/pnas.1910722117
Stéphanie Blockhuys,Xiaolu Zhang,Pernilla Wittung-Stafshede

Copper ions are needed for several hallmarks of cancer. However, the involved pathways, mechanisms, and copper-binding proteins are mostly unknown. We recently found that cytoplasmic Antioxidant 1 copper chaperone (Atox1), which is up-regulated in breast cancer, is localized at the lamellipodia edges of aggressive breast cancer cells. To reveal molecular insights into a putative role in cell migration, we here investigated breast cancer cell (MDA-MB-231) migration by video microscopy as a function of Atox1. Tracking of hundreds of individual cells (per condition) over a 9-h time series revealed that cell migration velocity and directionality are significantly reduced upon Atox1 silencing in the cells. Because silencing of the copper transporter ATP7A also reduced cell migration, these proteins appear to be on the same pathway, suggesting that their well-known copper transport activity is involved. In-cell proximity ligation assays demonstrated that Atox1, ATP7A, and the proenzyme of lysyl oxidase (LOX; copper-loaded via ATP7A) are all in close proximity and that LOX activity is reduced upon Atox1 silencing in the cells. Since LOX is an established player in cancer cell migration, our results imply that Atox1 mediates breast cancer cell migration via coordinated copper transport in the ATP7A-LOX axis. Because individual cell migration is an early step in breast cancer metastasis, Atox1 levels in tumor cells may be a predictive measure of metastasis potential and serve as a biomarker for copper depletion therapy.
更新日期:2020-01-29

 

全部期刊列表>>
施普林格自然
欢迎访问IOP中国网站
GIANT
自然科研线上培训服务
ACS ES&T Engineering
自然职场线上招聘会
ACS ES&T Water
产业、创新与基础设施
材料学研究精选
胸腔和胸部成像专题
屿渡论文,编辑服务
何川
苏昭铭
陈刚
姜涛
李闯创
北大
刘立明
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
天合科研
x-mol收录
上海纽约大学
曾林
天津大学
何振宇
史大永
吉林大学
卓春祥
张昊
杨中悦
试剂库存
down
wechat
bug