LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells

• DOI: 10.1083/jcb.201002041
• Publication Date: 2010-09-28T04:15:32Z
• Authors: Rebecca W. Scott; Steven Hooper; Diane Crighton; Ang Li; Ireen König; June Munro; Elisabeth Trivier; Grant Wickman; Pierre Morin; Daniel R. Croft; John Dawson; Laura Machesky; Kurt I. Anderson; Erik A. Sahai; Michael F. Olson
• Keywords: Cofilin; Invadopodia

LIM kinases 1 and 2 (LIMK1/2) are centrally positioned regulators of actin cytoskeleton dynamics. Using siRNA-mediated knockdown or a novel small molecule inhibitor, we show LIMK is required for path generation by leading tumor cells nontumor stromal during collective cell invasion. inhibition lowers cofilin phosphorylation, F-actin levels, serum response factor transcriptional activity collagen contraction, reduces invasion in three-dimensional assays. Although motility was unaffected, impairs matrix protein degradation invadopodia formation associated with significantly faster recovery times FRAP assays indicative reduced stability. When knocked down MDA-MB-231 cells, they lose the ability to lead strands collectively invading cells. Similarly, when blocked cancer-associated fibroblasts, unable squamous carcinoma an organotypic skin model. These results that remodeling activities