Abstract 2644: Investigating major vault protein promoting migration and its clinical relevance in oral squamous cell carcinoma

Abstract Introduction: Head and neck squamous cell carcinoma (HNSCC), particularly oral squamous cell carcinoma (OSCC), has emerged as a significant health concern in Taiwan. It is the sixth leading cause of cancer-related death in the country, posing major challenges to public health and healthcare systems. The limited treatment options for unresectable or metastatic HNSCC highlight the need for new therapeutic targets. Several studies have reported that major vault protein (MVP), the primary component of ribonucleoprotein particles known as vaults, plays a role in regulating drug resistance in cancer therapy. However, the effect of MVP on OSCC progression remains largely unknown. In this study, we investigated the mechanisms through which MVP contributes to OSCC progression and its impact on clinical outcomes. Materials and Methods: The migration ability of OSCC cells was assessed using wound-healing assays, two-chamber transwell invasion assays, and cell mobility tracking. Cisplatin resistance was evaluated using WST-1 cytotoxicity assays. Western blotting (WB), qRT-PCR, and RNA sequencing (RNA-seq) were conducted to explore potential mechanisms. Immunohistochemical (IHC) staining was used to determine MVP expression in OSCC tissues. Results: Analysis of the TCGA dataset showed that HNSCC patients with high MVP expression had lower overall survival rates. OSCC cells with MVP knockdown exhibited reduced migration ability, while cells with MVP overexpression demonstrated increased migration capacity compared to control cells in wound-healing, two-chamber transwell invasion assays, and cell mobility tracking. MVP knockdown in OSCC cells led to increased cisplatin sensitivity, whereas MVP overexpression resulted in cisplatin resistance, as demonstrated by WST-1 cytotoxicity assays. RNA sequencing data suggested that MVP may regulate cell differentiation, EGFR signaling, and cisplatin resistance, as indicated by GSEA analysis. Additionally, GO enrichment analysis suggested that MVP may influence the PI3K-AKT signaling pathway, focal adhesion, and ECM-receptor interaction. Western blotting assays confirmed that MVP overexpression in OSCC cells activated the PI3K-AKT-mTOR pathway. Furthermore, HNSCC patients with higher MVP expression levels or IHC H-scores were more likely to experience poorer recurrence-free survival. Conclusion: MVP may serve as a promising marker influencing clinical outcomes in HNSCC by regulating the PI3K-AKT-mTOR signaling pathway. Further validation of its clinical application is warranted. Citation Format: Sheng-Yen Hsiao, Shu-Fang Sun, Yuh-Ling Chen, Tse-Ming Hong. Investigating major vault protein promoting migration and its clinical relevance in oral squamous cell carcinoma [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 2644.