Improving fascin inhibitors to block tumor cell migration and metastasis

Molecular Oncology - Tập 10 - Trang 966-980 - 2016
Shaoqin Han1,2, Jianyun Huang2, Bingqian Liu2, Bowen Xing2, Francois Bordeleau3, Cynthia A. Reinhart-King3, Wenxin Li1, J. Jillian Zhang2, Xin-Yun Huang2
1College of Life Sciences, Wuhan University, Wuhan, China
2Department of Physiology and Biophysics, Cornell University, Weill Medical College, New York, NY 10065, USA
3Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA

Tóm tắt

Tumor metastasis is the major cause of mortality of cancer patients, being responsible for ∼90% of all cancer deaths. One of the key steps during tumor metastasis is tumor cell migration which requires actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are antenna‐like filopodia. Fascin protein is the main actin‐bundling protein in filopodia. Here we report the development of fascin‐specific small‐molecules that inhibit the interaction between fascin and actin. These inhibitors block the in vitro actin‐binding and actin‐bundling activities of fascin, tumor cell migration and tumor metastasis in mouse models. Mechanistically, these inhibitors likely occupy one of the actin‐binding sites, reduce the binding of actin filaments, and thus lead to the inhibition of the bundling activity of fascin. At the cellular level, these inhibitors impair actin cytoskeletal reorganization. Our data indicate that target‐specific anti‐fascin agents will have great potential for treating metastatic tumors.

Tài liệu tham khảo

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Molecular Oncology

Tập 10

966-980

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