Tks5 interactome reveals endoplasmic-reticulum-associated translation machinery in invadosomes

The ability to progress and invade through the extracellular matrix is a characteristic shared by both normal and cancer cells through the formation of structures called invadosomes, which include invadopodia and podosomes. These invadosomes are plastic and dynamic structures that can adopt different organizations-such as rosettes, dots, or linear invadosomes-depending on the cell types and the environment. In this study, we used the specific invadosome marker SH3 and PX domain-containing protein 2A (SH3PXD2A; also known as Tks5) to identify common features in these different organizations. Tks5 immunoprecipitation coupled with mass spectrometry analysis allowed us to identify common proteins in these different models. We identified elements of the translation machinery, in particular the eukaryotic translation initiation factor 4B (EIF4B) protein, but also endoplasmic reticulum (ER) proteins as part of the invadosome structure. Providing new data on invadosome molecular composition through the Tks5 interactome, we identified that ER-associated translation machinery is recruited to invadosomes and involved in their formation, persistence, and function in all types of invadosomes.