In this study, we found that wounding of a confluent monolayer of squamous cell carcinoma (SCC) cells induced epithelial–mesenchymal transition (EMT) specifically at the edge of the wound. This process required the combined stimulation of TGFβ, TNFα, and PDGF-D. Such a combined cytokine treatment of confluent monolayers of the cells upregulated the expression levels of Snail and Slug via PI3K. The PI3K downstream effector, AKT, was dispensable for the upregulation of Snail and Slug, but essential for enabling EMT in response to upregulation of Snail and Slug. J. Cell. Biochem. 114: 2039–2049, 2013. © 2013 Wiley Periodicals, Inc.