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. Key messages Loss of heterozygosity and stop-gain mutation of VPS52 were found in gastric cancer. Negative expression of VPS52 significantly correlated with poor prognosis. VPS52 inhibited viability and induced apoptosis of gastric cancer cells in vitro. VPS52 reduced tumor volume and tumor weight in vivo. VPS52 activated the apoptotic pathway through cathepsin D in gastric cancer cells.
[1]Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China.
[2]Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China.
(8.0+极速模式)