RAB14-dependent tubulovesicular recycling directs MET to invadopodia promoting TNBC cell invasion

Metastasis is one of the primary causes of cancer-related death in TNBC patients. During metastasis, stromal infiltration requires the cancer cells to form invadopodia, a membrane-protrusion with proteolytic activity. Cues from growth factors via the cognate RTKs promote invadopodia formation and cancer cell invasion. This study demonstrated the role of the HGF-MET axis in invadopodia formation and associated protease trafficking. MET interacts with MT1-MMP and is co-transported to the cell surface. Further, the RTK is found to reside at invadopodia, and its recruitment increases upon HGF stimulation due to enhanced recycling mediated by RAB4 and RAB14. The study further highlights the role of RCP in MET recycling by bringing RAB14 and MET together onto endosomal subdomains. KIF16B, a molecular motor, gets recruited to MET-containing endosomes via RAB14 and promotes the endosomal tubulation, which could be crucial for MET recycling.

Collectively, the study provides new insights into the mechanism of tubulovesicular recycling of MET and its implications in cancer cell invasion.