Abstract C49: Knockdown of FOXN2 enhances adhesion and reduces migration in pancreatic cancer cells

Abstract FOXN2, a member of the forkhead domain binding protein family, was identified as a master regulator whose expression and activity are increased in the progression from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDA). Forkhead transcription factor proteins have been identified as essential components of both oncogenic and tumor suppressive pathways. Deregulation of FOX proteins has a direct role in cancer initiation, maintenance, progression, and drug resistance. In particular, other studies have linked FOXN2 expression to better outcomes in T-cell leukemia and glioblastoma multiforme. Additionally, recent studies indicate that FOXN2 impairs lung cancer cell proliferation in vivo and in vitro. Finally, recent studies in breast cancer cells indicate potential conflicting roles for the FOXN2 transcription factor in maintenance of cancer stem cell phenotypes and in migration and invasion. In the present study, we sought to understand the role of FOXN2 specifically in human pancreatic malignancy. Data from the TCGA database indicates that high levels of FOXN2 are associated with poor overall survival. While knockdown of FOXN2 does not significantly affect proliferation or colony formation of pancreatic cancer cells, we report that knockdown of FOXN2 in PANC-1 and BxPC-3 cells significantly enhances cellular adhesion. Additionally, FOXN2 knockdown reduces cellular invasion through collagen in transwell migration assays. Preliminary data suggest that FOXN2 may mediate some of its effects on adhesion and migration through regulation of Akt2 expression. Overall, our studies suggest that high FOXN2 expression and activity contribute to pancreatic malignancy. A better understanding of the regulation and function of the FOXN2 transcription factor should help us to uncover its potential as a therapeutic target, as well as a predictive marker for cancer. Citation Format: Blanca Santibanez, Sabrina Oliveira, Kelsie Duggan, Kate Lu, Kristen Johnson. Knockdown of FOXN2 enhances adhesion and reduces migration in pancreatic cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C49.