In this study, we found that SYNJ2BP was activated via the PI3K/AKT/GSK3β/SNAI1 signaling pathway by the lysosome-mediated degradation of PTEN (a novel degradation mechanism of PTEN), which then resulted in changes in the EMT phenotype and the subsequent promotion of invasiveness and metastasis of breast cancer cells in vivo and vitro. Moreover, SYNJ2BP expression levels in breast carcinoma patients was statistically associated with tumor stage. This evidence concerns the gene GSK3B and breast cancer.