Fig. 9: Overall view of how DRAM1 prevents the ubiquitination of VAMP8 to increase autolysosome formation and promotes the extravasation of HCC cells.

In the absence of DRAM1: DRAM1 deficiency leads to CHIP directly binding with VAMP8, which contributes to ubiquitination and degradation of VAMP8, eventually causing the decreased assembly of STX17-SNAP29-VAMP8 complex and inhibition of the autolysosome formation, which leads to inhibiting the extravasation of HCC cells. In the presence of DRAM1: DRAM1 interacts with VAMP8 on the lysosome membrane and inhibits CHIP binding with VAMP8, which results in reduced ubiquitination of VAMP8 and enhances the stabilization of the STX17-SNAP29-VAMP8 complex, facilitating the autolysosome formation and eventually promotes the extravasation of HCC cells.