Abstract
Epithelial-mesenchymal transition (EMT) is a critical stage in the metastasis of gastric cancer (GC). Further clarification of the EMT process in GC is still needed. This study examined the effects of the NEDD4L/BICC1 axis on GC proliferation and the EMT process. Thirty GC patients were enrolled in this study to assess the expression of BICC1 and NEDD4L in tumor samples. A xenograft tumor model in mice was created to investigate BICC1's function in vivo. The proliferation, migration, and invasion of GC cells were evaluated using colony formation, transwell, and wound healing assays. Western blot determined the expression levels of EMT-associated proteins. Co-immunoprecipitation (Co-IP) elucidated the mechanism by which NEDD4L regulates BICC1. BICC1 was found to be overexpressed in tumors. Additionally, BICC1 knockdown inhibited the growth of GC cells in vivo and prevented their migration, invasion, proliferation, and EMT. Furthermore, BICC1 activated the PI3K/AKT pathway, which facilitated cancer progression. Tumor tissues and GC cells exhibited low expression levels of NEDD4L. Conversely, NEDD4L overexpression promoted the ubiquitination and degradation of BICC1 protein, thereby inhibiting GC cell proliferation, migration, invasion, and EMT processes. Our study demonstrated that NEDD4L acts as a tumor suppressor in GC, while BICC1 functions as a pro-tumorigenic factor. The NEDD4L/BICC1 axis plays a significant role in the metastasis and progression of GC.