Mechanisms and roles of podosomes and invadopodia

Podosomes and invadopodia, collectively called 'invadosomes', are actin-based structures that drive proteolytic invasion in various physiologically relevant cell types (including osteoclasts, immune cells, endothelial cells and fibroblasts) and in cancer cells. Recent work has expanded our understanding of the architecture and mechanisms of invadosomes, and has revealed their diverse functions beyond matrix degradation. Cell invasion into the surrounding extracellular matrix or across tissue boundaries and endothelial barriers occurs in both physiological and pathological scenarios such as immune surveillance or cancer metastasis. Podosomes and invadopodia, collectively called 'invadosomes', are actin-based structures that drive the proteolytic invasion of cells, by forming highly regulated platforms for the localized release of lytic enzymes that degrade the matrix. Recent advances in high-resolution microscopy techniques, in vivo imaging and high-throughput analyses have led to considerable progress in understanding mechanisms of invadosomes, revealing the intricate inner architecture of these structures, as well as their growing repertoire of functions that extends well beyond matrix degradation. In this Review, we discuss the known functions, architecture and regulatory mechanisms of podosomes and invadopodia. In particular, we describe the molecular mechanisms of localized actin turnover and microtubule-based cargo delivery, with a special focus on matrix-lytic enzymes that enable proteolytic invasion. Finally, we point out topics that should become important in the invadosome field in the future.

Automated summary

Invadosomes are actin-based structures that drive cellular invasion by degrading the extracellular matrix. Recent research has provided new insights into the architecture and functions of invadosomes, and advancements in imaging techniques have further improved our understanding of these structures.