The MARCH ubiquitin ligase family has a role in degrading membrane molecules, and MARCH8 is an E3 ligase that ubiquitinates DR4 for subsequent lysosomal degradation.32 Our results indicated that JWA induced ubiquitin-dependent lysosomal degradation of DR4 via the upregulation of MARCH8 expression, thereby decreasing the sensitivity of GC cells to TRAIL. This evidence concerns the gene ARL6IP5 and gastric cancer.