Integrin-mediated interactions between the extracellular matrix and the actin cytoskeleton play a central role in regulating cell migration in both normal and pathological processes, such as tumor metastasis. Many adherent cell types, such as fibroblasts, form integrin-mediated adhesions, known as focal adhesions, that undergo cycles of assembly and disassembly during cell migration. Focal adhesions are generally found in less motile cells and function to tether actin-containing stress fibers. In contrast, motile and invasive cells, including myeloid cells and invasive cancer cells, frequently form specialized integrin-mediated adhesive structures known as podosomes or matrix-degrading invadopodia (Buccione et al., 2004; Linder, 2007). Dynamic regulation of invadopodia in carcinoma cells is likely critical for the invasive capacity of metastatic cancer cells. However, an understanding of the mechanisms that regulate invadopodia dynamics in cancer cells remains limited.

First identified in fibroblasts transformed with the Roussarcoma virus v-Src oncogene (Tarone et al., 1985), podosomes and invadopodia contain many of the cytoskeletal and signaling proteins found in focal adhesions, including talin, vinculin, and paxillin (Linder and Aepfelbacher, 2003). In contrast to focal adhesions, podosomes and invadopodia are not associated with stress fibers but instead contain several actin regulatory proteins, including cortactin, gelsolin, Wiskott-Aldrich syndrome protein, and the actin-nucleating Arp 2/3 complex (Buccione et al., 2004). Furthermore, a hallmark of the invasive podosomes or invadopodia formed in metastatic cancer cells is the capacity for matrix degradation through the localized secretion of ECM-degrading matrix metalloproteases (Linder and Aepfelbacher, 2003).