CAP1 signaling regulates tumor immunity, proliferation, and migration in esophageal cancer

Abstract Objectives Esophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. Our study aimed to explore the regulatory pathways of CAP1 in ESCA and its effects on tumor immunity. Methods Immune-related differentially expressed genes (DEGs) associated with ESCA prognosis were screened through bioinformatics analysis, and a risk prognosis model was constructed. In addition, we employed a combination of in vitro techniques, including qRT-PCR, Western blot, CCK-8, Transwell, co-culture, CHIP, and dual-luciferase reporter assays, to systematically investigate the expression, function, and transcriptional regulation of CAP1 in ESCA. Furthermore, the role of the ELF1/CAP1 axis was verified using a xenograft tumor model. Results Bioinformatics analysis using LASSO Cox regression demonstrated that CAP1 carried the highest risk coefficient (0.4437) in the prognostic model. The risk score model demonstrated excellent predictive performance in the TCGA cohort and was successfully validated in external GEO datasets. High expression of CAP1 in ESCA cells enhanced their proliferative, migratory, and invasive capabilities (p<0.001). In a co-culture system, silencing CAP1 in ESCA cells enhanced the cytotoxicity of CD8+ T cells and reduced their apoptosis (p<0.001). The transcription factor ELF1 promoted CAP1 expression by binding to its promoter, thereby regulating immune evasion and tumor progression in ESCA. Importantly, in vivo experiments confirmed that knockdown of either ELF1 or CAP1 significantly suppressed tumor growth, enhanced CD8+ T cell infiltration, and downregulated PD-L1 expression (p<0.001), demonstrating that ELF1 promotes tumor progression and immune escape in ESCA via CAP1. Conclusion CAP1 promotes ESCA progression by regulating tumor immunity, cell proliferation, and migration. ELF1 plays a crucial role in ESCA by transcriptionally regulating CAP1 expression. These findings identify the ELF1/CAP1 axis as a promising therapeutic target and prognostic biomarker for ESCC.