Tks5 interactome reveals ER-associated machinery translation in invadosomes

Abstract 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 gathering invadopodia and podosomes. These invadosomes are plastic and dynamic structures that can adopt different organizations depending on the cell types and the environment such as rosettes, dots or linear invadosomes. In this study, we used the specific invadosome marker Tks5 (SH3PXD2A), 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 EIF4B protein, but also endoplasmic reticulum (ER) proteins as part of the invadosome structure. Providing new data on invadosome molecular composition through Tks5 interactome, we identified that ER-associated translation machinery is recruited to invadosome and involved in their formation, persistence and function in all types of invadosomes. Summary Invadosomes are invasive F-actin structures exhibiting different organizations that degrade the extracellular matrix. The study uses their universal marker, Tks5, to provide new data about invadosome molecular composition and reveal the role of ER-associated translation machinery in invadosome formation and function. Competing Interest Statement The authors have declared no competing interest. Footnotes The text has been edited for clarity. Discussion has been improved Experiments have been added (Figure 6b and Supp Fig 3g) Abbreviations - CHX - cycloheximide - ECM - extracellular matrix - EIF4B - eukaryotic translation initiation factor - 4B ER - endoplasmic reticulum - RPS6 - ribosomal subunit S6