Biology subjects

BONNARD, B.

Publications and source records attributed to BONNARD, B..

2 recordsLinked to original sources

bioRxiv2024

Src promotes tumor cell invasion by hijacking the translation machinery

The Src oncogene controls cancer cell invasiveness by promoting invadosome formation and extracellular matrix degradation (ECM). Invadosomes are enriched in the eukaryotic translation initiation factor 3 (eIF3) complex associated with a local mRNA translation activity mandatory for their maintenance. Here, we show that Src regulates mRNA translation by controlling the expression of eIF3 subunits. Among them, eIF3h/e/d are essential for invadosome formation and ECM degradation. We demonstrate that Src controls the canonical mTOR/eIF4E and the non-canonical eIF3d cap-dependent translation initiation pathways. We show that both pathways are necessary for invadosome formation and their ECM degradation function. Finally, we highlighted a correlation between Src and eIF3h/e/d overexpression, which is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and controls the ECM degradation and invasive properties of HCC cells. These findings identify Src as a major regulator of translation initiation pathways, which leads to invadosome formation, ECM degradation and tumor cell invasion. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/606119v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1804203org.highwire.dtl.DTLVardef@16ddae8org.highwire.dtl.DTLVardef@13ecca5org.highwire.dtl.DTLVardef@1ed685a_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

cell biology↗

bioRxiv2024

Tks5 interactome reveals ER-associated machinery translation 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 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. SummaryInvadosomes 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.

cancer biology↗