The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function

Key Points Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane. They act as sites of attachment to — and degradation of — the extracellular matrix. These structures contain actin regulators such as cortactin and neural Wiskott–Aldrich syndrome protein (N-WASP), adaptor proteins such as Tyr kinase substrate with four SH3 domains (TKS4) and Tyr kinase substrate with five SH3 domains (TKS5), and several pericellular proteases. Podosomes are found in vascular smooth muscle and endothelial cells, as well as in cells derived from monocyte lineages. Their presence correlates with migratory ability. Invadopodia are found in invasive human cancer cells. In two-dimensional culture, their presence correlates with invasive behaviour. However, in three-dimensional culture and in vivo , invadopodium-associated proteins are also required for cell growth. Podosome-associated proteins have been implicated in human developmental and immune disorders, and dysregulation of podosome formation is associated with atherosclerosis. Small-molecule regulation of podosomes and invadopodia might represent a new therapeutic strategy to treat several diseases. Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to — and degradation of — the extracellular matrix. Progress has been made in our understanding of the regulation and function of these structures, and their role in human disease. Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to — and degradation of — the extracellular matrix. The key proteins in these structures include the actin regulators cortactin and neural Wiskott–Aldrich syndrome protein (N-WASP), the adaptor proteins Tyr kinase substrate with four SH3 domains (TKS4) and Tyr kinase substrate with five SH3 domains (TKS5), and the metalloprotease membrane type 1 matrix metalloprotease (MT1MMP; also known as MMP14). Many cell types can produce these structures, including invasive cancer cells, vascular smooth muscle and endothelial cells, and immune cells such as macrophages and dendritic cells. Recently, progress has been made in our understanding of the regulatory and functional aspects of podosome and invadopodium biology and their role in human disease.