Abstract 81: FOXN3 suppresses FUT5-mediated adhesion of metastatic ovarian cancer cells to mesothelial cells

Abstract Ovarian cancer is the most lethal gynecological malignancy primarily due to widespread peritoneal metastasis at diagnosis, posing significant treatment challenges. Our previous research has indicated that fucosyltransferase 5 (FUT5) is upregulated in metastatic ovarian cancer and is a key contributor to peritoneal metastatic colonization, which represents the initial rate-limiting step in metastasis. However, little is known about the regulation of FUT5. In this study, using a microfluidic chip model with ascitic fluid shear stress perfusion, we found that FUT5 is transcriptionally upregulated in ovarian cancer cells treated with ascitic shear stress, with no changes in degradation rates of FUT5 protein and transcript. Through a comprehensive analysis involving transcriptional factor prediction, biostatistics on TCGA database expression patterns, and sequence analysis using a metastatic cancer model, we identified Forkhead Box N3 (FOXN3) as a potential regulator of FUT5 transcription. Further investigation demonstrated that FOXN3 suppresses FUT5 expression by directly interacting with its promoter. Expression of FOXN3 suppresses tumor-mesothelial adhesion, which can be reversed by FUT5 overexpression. Together, these findings suggest that the FOXN3/FUT5-axis plays a crucial role in ovarian tumor-mesothelial interaction and could serve as a potential therapeutic target (This work is supported by HMRF08192286 and RGC SRFS2223-7S05). Citation Format: Siyu Zhou, Ayon Ahmed Hassan, Alice Sze Wong. FOXN3 suppresses FUT5-mediated adhesion of metastatic ovarian cancer cells to mesothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 81.