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 by Transwell invasion and 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 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.