In the present study, using CD82 loss- and gain-of function approaches on three human prostate cancer cell lines with invasive and metastatic potential, we identified CD82 as a potent inhibitor of matrix adhesion-dependent EMT in prostate cancer cells, providing a clue for understanding how CD82 suppresses the tumor cell-intrinsic invasive and metastatic potential. The gene discussed is CD82; the disease is prostate cancer.