SCAI (suppressor of cancer cell invasion), has been recently characterized as a novel tumor suppressor that inhibits the invasive migration of several human tumor cells. However, the expression pattern, biological role and molecular mechanism of SCAI in human glioma remain unknown. In this study, we found that levels of SCAI protein and mRNA expression were significantly downregulated in glioma tissues and cell lines. Overexpression of SCAI inhibited, but silencing of SCAI robustly promoted the invasive and cancer stem cell-like phenotypes of glioma cells. Furthermore, we demonstrated that SCAI downregualtion activated the Wnt/beta-catenin signaling, and blockade of the Wnt/beta-catenin pathway abrogated the effects of SCAI downregulation on glioma cell aggressiveness. Taken together, our results provide the first demonstration of SCAI downregulation in glioma, and its downregulation contributes to increased glioma cell invasion and self-renewal by activating the Wnt/beta-catenin pathway. (C) 2014 Elsevier Inc. All rights reserved.