E2F7 promotes ESCC progression and cisplatin resistance through transcriptional activation of DVL3 and the Wnt signaling pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor prognosis. While the transcription factor E2F7 has been implicated in cancer development, its specific role in ESCC and its association with cisplatin resistance remain unclear. This study aimed to investigate the expression, function, and underlying mechanism of E2F7 in ESCC progression and cisplatin resistance.

METHODS: E2F7 expression was examined in ESCC tissues and cell lines using qRT-PCR, and its clinical significance was assessed through survival analysis. Functional roles of E2F7 were evaluated through cell proliferation, migration, and invasion assays. Mechanistic studies included dual-luciferase reporter assays and gene expression analyses to assess E2F7's regulation of DVL3 and activation of the Wnt signaling pathway. The impact of E2F7 on cisplatin sensitivity and apoptosis was also investigated.

RESULTS: E2F7 was significantly upregulated in ESCC tissues and cell lines, and its high expression was associated with advanced tumor stage, metastasis, and poor patient survival. E2F7 overexpression promoted ESCC cell proliferation, migration, and invasion, while knockdown suppressed these malignant behaviors. Mechanistically, E2F7 directly activated DVL3 transcription, thereby activating the Wnt pathway activity. Silencing DVL3 partially reversed the tumor-promoting effects of E2F7. Furthermore, E2F7 knockdown increased cisplatin sensitivity and induced apoptosis, which were reversed by DVL3 overexpression. However, direct ChIP evidence of E2F7 binding to the DVL3 promoter is lacking, representing a limitation of this study.

CONCLUSIONS: E2F7 promotes ESCC progression and cisplatin resistance by transcriptionally activating DVL3 and activating the Wnt signaling pathway. Targeting the E2F7-DVL3 axis may provide a promising therapeutic strategy for ESCC treatment.