nsition through Phosphorylation of Snail

nloaded cer cells undergo epithelial-mesenchymal transition (EMT) as a program of increased invasion and tasis during cancer progression. Here, we report that a novel regulator of EMT in cancer cells is protein D1 (PKD1), which is downregulated in advanced prostate, breast, and gastric cancers. Ectopic reexpresf PKD1 in metastatic prostate cancer cells reversibly suppressed expression of mesenchyme-specific and increased epithelial markers such as E-cadherin, whereas small interfering RNA–mediated knockof PKD1 increased expression of mesenchyme markers. Further, PKD1 inhibited tumor growth and tasis in a tumor xenograft model. PKD1 phosphorylates Ser (S11) on transcription factor Snail, ter EMT regulator and repressor of E-cadherin expression, triggering nuclear export of Snail via 14-3ding. Snail S11 mutation causes acquisition of mesenchymal traits and expression of stem cell markers. her, our results suggest that PKD1 functions as a tumor and metastasis suppressor, at least partly Toget by regulating Snail-mediated EMT, and that loss of PKD1 may contribute to acquisition of an aggressive malignant phenotype. Cancer Res; 70(20); 7810–9. ©2010 AACR.