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Sci. Signal., 26 July 2011
Vol. 4, Issue 183, p. ra49
Finding Targets for Inhibiting Cancer Cell Metastasis
Cancer cells escape from the primary tumor site in part because of invadopodia, actin-rich, foot-like cellular processes that degrade the surrounding extracellular matrix (ECM). Invasiveness of cancer cells is often correlated to the presence of invadopodia. Quintavalle et al. developed a high-throughput method of screening the effects of compounds on the formation of invadopodia and ability to degrade the ECM. They found that the chemotherapeutic agent paclitaxel increased the formation of invadopodia and ability to degrade the ECM, suggesting that its use might promote invasiveness, especially if used before the main therapy or in patients with tumors resistant to the cytotoxicity of this drug. In contrast, invasive behavior was inhibited by a group of compounds that inhibited the cyclin-dependent kinase Cdk5, which was found to phosphorylate the actin regulatory protein caldesmon, thereby triggering its degradation and leading to the formation of invadopodia. Thus, these results identify potential undesirable cellular effects of a chemotherapeutic agent and a possible therapeutic target for restricting invasiveness in cancer cells.
Citation: M. Quintavalle, L. Elia, J. H. Price, S. Heynen-Genel, S. A. Courtneidge, A Cell-Based High-Content Screening Assay Reveals Activators and Inhibitors of Cancer Cell Invasion. Sci. Signal.4, ra49 (2011).