Degrading Devices: Invadosomes in Proteolytic Cell Invasion

Abstract

Podosomes and invadopodia, collectively known as invadosomes, are cell-matrix contacts in a variety of cell types, such as monocytic cells or cancer cells, that have to cross tissue barriers. Both structures share an actin-rich core, which distinguishes them from other matrix contacts, and are regulated by a multitude of signaling pathways including RhoGTPases, kinases, actin-associated proteins, and microtubule-dependent transport. Invadosomes recruit and secrete proteinases and are thus able to lyse extracellular matrix components. They are therefore considered to be potential key structures in proteolytic cell invasion in both physiological and pathological settings. This review provides an overview of the field, with special focus on current developments such as intracellular transport processes, ultrastructural analysis, the possible involvement of invadosomes in disease, and the tentative identification of invadosomes in 3D environments and in vivo.

CDCP1 Regulates the Function of MT1-MMP and Invadopodia-Mediated Invasion of Cancer Cells

“…Surface MT1-MMP is internalized by clathrin-and caveolin-dependent endocytosis and is then degraded in lysosomes or recycled back to the plasma membrane (27). Recent studies have revealed that the targeted delivery of MT1-MMP to invadopodia through membrane trafficking is necessary for its accumulation and proteolytic activity in these structures (21,22,30,31). In addition, we previously reported that caveolin-1 colocalizes and traffics with MT1-MMP and controls the MT1-MMP-dependent degradation of the ECM at invadopodia (29).…”

“…Recent studies have shown that targeted trafficking of MT1-MMP to invadopodia, which is mediated by vesicleassociated membrane protein 7, the exocyst complex, caveolin-1, and lipid rafts, is crucial for its accumulation and matrix degradation activity at invadopodia (21,22,(29)(30)(31). Therefore, we next examined the effect of CDCP1 knockdown on the localization of MT1-MMP at invadopodia.…”

“…Invadopodia are unique protrusions observed at the cell adhesion sites of invasive cancer cells that are rich in cell-ECM adhesion molecules, actin assembly regulators, membrane-remodeling proteins, tyrosine kinases, tyrosine-phosphorylated proteins, and MMPs (22,23). Because they offer an environment that supports ECM degradation and thus cancer invasion and metastasis, the ability to form invadopodia is closely associated with the invasive and metastatic potentials of cancer cells (24,25).…”

The interplay between the proteolytic, invasive, and adhesive domains of invadopodia and their roles in cancer invasion

“…They can be located throughout the cell in marcrophages, located at the cell periphery in smooth muscle cells, forming rosette-shaped clusters in endothelial cells, and in unique super-structures, such as sealing zones, in osteoclasts. 4 Src-induced invadosomes in fibroblasts display rosette-shaped peripheral invadosomes. 4 Invadopodia are long-lived, stable structures that last up to a few hours, 27,28 as opposed to podosomes, whose lifespans is in the order of few minutes.…”

“…26 Despite the overall similarity between invadopodia, podosomes, and src-induced invadosomes, they do vary in their size, shape, density, and stability. 1,4 Under a fluorescent microscope, invadopodia of cultured cancer cells usually appear as dot-like structures, with an F-actin core, containing several actin-binding proteins and signaling molecules. 2,5 The cores can be scattered or clustered at the cell center, usually in close proximity to the nucleus.…”