B-359 Bap1 Overexpression Enhances Epithelial-mesenchymal Transition in Cholangiocarcinoma

Abstract

Abstract Background BRCA1-associated protein 1 (BAP1) is a nuclear protein that considered as a tumor suppressor by its involvement in DNA double-strand-break repair. However, BAP1 overexpression was observed in many kinds of cancer, such as intrahepatic cholangiocarcinoma (iCCA). Methods and Results Formalin-fixed paraffin-embedded cancer tissues were acquired from the archive of the Department of Pathology, Chang Gung Memorial Hospital at Kaohsiung, Taiwan. In this study, we identified 23.8% cytoplasmic BAP1 overexpression and 20.8% nuclear BAP1 overexpression cases in 101 iCCA patients. There were significant correlations between cytoplasmic expression of BAP1 with tumor growth pattern (P = 0.005), T classification (P = 0.006), and clinical AJCC seventh staging (P < 0.001). In cell models (iCCA cell line RBE), overexpressed BAP1 were accumulated in cytoplasm. The translatome profile suggested that BAP1 overexpression may promote the migratory and invasive capacities of iCCA cells. In-vitro assays validated that BAP1 overexpression enhanced cell migration and invasion. Furthermore, we found that BAP1 overexpression induced epithelial-mesenchymal transition (EMT) in iCCA cells, showing E-cadherin and fibronection down-regulation and vimentin up-regulation. Conclusion These findings indicated that cytoplasmic BAP1 overexpression increased migratory and invasive capacities in iCCA cells, at least in part, via enhanced EMT regulations. Based on these findings, cytoplasmic BAP1 expression could be a candidate predictor for metastasis of iCCA.