MAGEA11 promotes GC proliferation, migration, and invasion through activation of E2F1 transcriptional activity

Gastric cancer (GC) is a prevalent gastrointestinal malignancy in China. Despite advancements in multidisciplinary diagnosis and treatment strategies, the 5-year survival rate remains low at just 10-20%. A significant number of patients ultimately die from postoperative recurrence and distant metastasis. Therefore, it is crucial to investigate the core mechanisms underlying GC development and progression and to identify potential molecular targets for early diagnosis, prevention, and treatment. MAGEA11, part of the melanoma-associated antigen (MAGE) gene family, is associated with several cancers. However, its expression, function, and mechanisms in GC remain unclear. In this study, we first confirmed that MAGEA11 is highly expressed in GC through data analysis from The Cancer Genome Atlas (TCGA), univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curve analysis. Our findings indicate that MAGEA11 is an independent prognostic factor for overall survival (OS) in GC patients, with higher expression levels correlating with shorter OS, disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Next, we explored the role of MAGEA11 in GC by constructing stable cell models with MAGEA11 knockdown and overexpression. Functional assays on these models demonstrated that MAGEA11 promotes the proliferation, migration, and invasion of GC cells in vitro. Additionally, the tumor-promoting effects of MAGEA11 were verified in vivo using a GC cell tumor model. Previous studies have shown that MAGEA11 increases the transcriptional activity of the transcription factor E2F1, thereby promoting cancer progression. To verify this mechanism in GC, we conducted cell function experiments and immunohistochemistry, confirming that MAGEA11 promotes GC development by activating E2F1's transcriptional activity. These findings indicate that MAGEA11 may be a useful molecular marker for predicting GC prognosis.