We have previously demonstrated that the peptide mimicking small extracellular ring domain of CD82 (CD82EC1-mP) could inhibit tumor cell motility and metastasis. However, its acting mechanism is not understood. Here, we reported that the cell motility-inhibitory function of CD82EC1-mP was involved in the downregulation of epithelial-mesenchymal transition (EMT). Both vimentin and E-cadherin are EMT makers. We found that CD82EC1-mP could inhibit the expression of vimentin, but promot the expression of E-cadherin, suggesting that CD82EC1-mP suppressed EMT. Hippo/YAP and Wnt/beta-catenin are both key signal pathways that regulate the EMT process. The futher studies showed that CD82EC1-mP couled activate GSK3 beta, promote the phosphorylation of beta-catenin, and inhibit the beta-catenin nuclear location. Moreover, CD82EC1-mP couled activate Hipoo kinase cascade, promote the phosphorylation of YAP, and inhibit the YAP nuclear location. These results suggested that CD82EC1-mP inhibited invation and matestasis via inhibiting EMT through downregulating Wnt pathway and upregulating Hippo pathway. (C) 2020 Elsevier Inc. All rights reserved.