Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

Fang-Ke Huang, Shaoqin Han, Bowen Xing, Jianyun Huang, Bingqian Liu, Francois Bordeleau, Cynthia A. Reinhart-King, J. Jillian Zhang and Xin-Yun Huang ()
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Fang-Ke Huang: Cornell University Weill Medical College
Shaoqin Han: Cornell University Weill Medical College
Bowen Xing: Cornell University Weill Medical College
Jianyun Huang: Cornell University Weill Medical College
Bingqian Liu: Cornell University Weill Medical College
Francois Bordeleau: Cornell University
Cynthia A. Reinhart-King: Cornell University
J. Jillian Zhang: Cornell University Weill Medical College
Xin-Yun Huang: Cornell University Weill Medical College

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract One of the key steps during tumour metastasis is tumour cell migration and invasion, which require actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are the filopodia, which act like cell sensory organs to communicate with the extracellular microenvironment and participate in fundamental cell functions such as cell adhesion, spreading and migration in the three-dimensional environment. Fascin is the main actin-bundling protein in filopodia. Using high-throughput screening, here we identify and characterize small molecules that inhibit the actin-bundling activity of fascin. Focusing on one such inhibitor, we demonstrate that it specifically blocks filopodial formation, tumour cell migration and invasion in vitro, and metastasis in vivo. Hence, target-specific anti-fascin agents have a therapeutic potential for cancer treatment.

Date: 2015
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DOI: 10.1038/ncomms8465

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