VPS52 induces apoptosis via cathepsin D in gastric cancer

Vacuolar protein sorting (vps) genes encode a class of proteins involved in vesicular trafficking. growing evidence suggests that vps proteins play roles in tumor biology. vacuolar protein sorting 52 (vps52) is involved in retrograde transport of endosomes, and its roles in cancers have not been explored. this study investigated the genetic alterations, protein changes, biological role, and molecular mechanism of vps52 in gastric cancer. loss of heterozygosity of vps52 was detected in 52.9% (9/17) of gastric cancer samples. twenty-five percent (5/20) gastric cancer samples contained somatic stop-gain mutation of vps52, two of which also had simultaneous loss of heterozygosity. lack of vps52 protein expression in gastric cancer tissue was found compared with pericancerous tissue and was significantly correlated with more advanced tnm staging and shorter 3-year overall survival. overexpression of vps52 significantly reduced viability and increased apoptosis in gastric cancer cells in vitro and reduced tumor volume and tumor weight in xenograft model in vivo. activation of the cathepsin d/bax/cytochrome c/caspase 9/caspase 3 pathway was detected in gastric cancer cells overexpressing vps52. collectively, vps52 is a tumor suppressor gene in gastric cancer and could be used as a biomarker. vps52 adenovirus could be a novel anti-tumor reagent for future gene therapy.