Nectin-4 promotes gastric cancer progression via the PI3K/AKT signaling pathway

Nectin-4, a member of the Nectin family that includes 4 Ca⁺-independent immunoglobulin-like cell adhesion molecules, plays a carcinogenic role in multiple cancers. However, Nectin-4 expression and its biological role in gastric cancer (GC) remain largely unknown. In this study, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to evaluate the expression patterns of Nectin-4 in GC specimens and cell lines. We observed that high expression of Nectin-4 in GC patients was associated with TNM stage and lymph node metastasis status, and poor prognosis. In addition, cell proliferation and cell migration assays in vitro and tumorigenicity in vivo were performed to observe the effects of up-regulation and down-regulation of Nectin-4 expression on GC cell phenotypes. In further studies, the PI3K/AKT signaling pathway was revealed to be involved in Nectin-4-mediated GC progression. These results demonstrated that Nectin-4 had a promoter effect on human GC cell growth and motility, indicating that Nectin-4 may serve as an effective therapeutic target in GC.