Contributed Talk

Distinct F-actin networks are required for filopodia motility and migration of cancer cells

Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany

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Cellular migration and invasion are essential steps in the metastatic cascade of tumor cells, and depend on tight regulation of cytoskeletal actin dynamics. Our group identified an actin cross-linking protein essentially involved in the control of actin dynamics and metastasis of lung cancer cells. This protein Ins(1,4,5)P3-kinase-A (ITPKA) binds to F-actin via one N-terminal actin binding domain, and by forming homodimers, it bundles F-actin. In concert with the C-terminal Ins(1,4,5)P3-kinase domain, ITPKA finally induces the formation of tight flexible F-actin networks. Recently, we found that these F-actin networks are required for filopodia motility, and for ITPKA-stimulated migration and invasion. Thus, blocking the interaction between ITPKA and F-actin may inhibit the metastasis-promoting activity of ITPKA.