Abstract Background: Glioblastoma multiforme (GBM) is the most common and lethal primary human brain tumor and exhibits multiple molecular aberrations. In this study, we attempted to explore the role of a nuclear transport receptor RanBP17 in carcinogenesis and its underlying mechanisms in GBM. Methods: The relevant information retrieved from the Human Integrated Protein Expression Database (HIPED), TCGA, and Rembrandt was analyzed to evaluate and compare RanBP17 expression in various tissues and cancer types. Next U87 and U251 were used to investigate the effects of RPS15A on epithelial-mesenchymal transition (EMT) and malignant behaviors of glioma cells. Further, RPS15A-associated signaling pathways were screened based on the data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and verified by using RT-PCR and Western blot (WB) assays. Results: RanBP17 was highly expressed in normal brain tissue, and loss or downregulation of RanBP17 was observed in GBM tissue (83/105, 79.05%) and associated with worse survival of patients. Overexpression of RanBP17 suppressed proliferation, migration and invasion of GBM cells in vitro and remarkably inhibited tumor growth in vivo. In addition, RanBP17 silencing promoted EMT of glioma cells via activating the expression of transcriptional factor Snail. Further experiments confirmed that RanBP17 overexpression promoted the export of β-catenin from cell nuclei and retarded wnt/β-catenin signaling. Conversely, knockdown of RanBP17 gene resulted in accumulation of β-catenin in glioblastoma cell nuclei, which, in turn, promoted expression of EMT-related proteins and malignant progression of glioblastoma by combining other transcript genes. Conclusions: RanBP17 expression is significantly lower in GBM compared to normal brain tissue. Silencing RanBP17 accelerates the EMT process and malignant progression of glioblastoma due to the suppressed export of β-catenin from glioblastoma cell nuclei and the resulting inhibition of wnt/β-catenin signaling. Therefore, loss or downregulation of RanBP17 can be considered a negative prognostic factor for survival of GBM patients. Citation Format: Yi Wang, Penyi Guo, Xiaozai Xie, Sina Zhang, Haitao Yu, Lijun Wu, Ziyan Chen, Gang Chen. RanBP17 retards the epithelial-mesenchymal transition (EMT) and malignant progression of glioblastoma cells by regulating the exportation of beta-catenin from cell nucleus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2482.