MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion

被引:102
作者
Bockhorn, Jessica [1 ,2 ]
Yee, Kathy [1 ]
Chang, Ya-Fang [1 ]
Prat, Aleix [3 ]
Huo, Dezheng [4 ]
Nwachukwu, Chika [5 ]
Dalton, Rachel [1 ]
Huang, Simo [1 ]
Swanson, Kaitlin E. [1 ]
Perou, Charles M. [3 ]
Olopade, Olufunmilayo I. [5 ]
Clarke, Michael F. [6 ]
Greene, Geoffrey L. [1 ]
Liu, Huiping [1 ,6 ]
机构
[1] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[4] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA
[5] Univ Chicago, Ctr Clin Canc Genet, Dept Med, Chicago, IL 60637 USA
[6] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA
基金
美国国家卫生研究院;
关键词
miR-30c; Breast tumor invasion; TWF1; VIM; IL-11; STEM-CELLS; TWINFILIN; ROLES; STAT3; WAR;
D O I
10.1007/s10549-012-2346-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Metastasis remains a significant challenge in treating cancer. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients.
引用
收藏
页码:373 / 382
页数:10
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