Increasing expression of presenilin 1, β-catenin, and p-PTEN and its regulatory roles on cell invasion in gastric cancer

BACKGROUND Presenilin-1 (PS-1), a part of the gamma-secretase complex, has been implicated as a tumor promoter in various cancers. PS-1 binds to β-catenin through a large hydrophilic loop region that could lead to gastric tumorigenesis by the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway, which is known to inhibit phosphatase and tensin homolog deleted on chromosome ten (PTEN). However, little is known about the mechanisms of PS-1, β-catenin, and PTEN in gastric cancer (GC) tumorigenesis. AIM To determine the regulatory correlation among PS-1, β-catenin, and phosphorylation of PTEN (p-PTEN) in GC tumorigenesis . METHODS Tissue samples from 116 patients with GC were analyzed by immunohistochemistry. Cell lysates from MGC-803 were used to detect protein levels by western blot. Cell invasion ability and metastatic ability were examined in vitro by Transwell invasion and in vivo via tail vein injection, respectively. RESULTS The high expression rates of PS-1, β-catenin, and p-PTEN in GC were 60.3% (70/116), 56.9% (66/116), and 47.4% (55/116), respectively, correlating with advanced tumor stages based on tumor invasion, lymph node metastasis, and 5-year survival. PS-1 expression was positively correlated with expression of β-catenin and p-PTEN in patients with GC. PS-1 regulated PTEN phosphorylation and cytoplasmic localization through β-catenin. PS-1 enhanced GC cell invasion via β-catenin. CONCLUSION The expression of PS-1 was positively correlated with that of both β-catenin and p-PTEN in GC. The regulation of PTEN phosphorylation and cytoplasmic localization by PS-1 through β-catenin could be considered potential therapeutic targets to prevent GC tumorigenesis.