SMURF1 leads to the β-catenin signaling-mediated progression of esophageal squamous carcinoma by losing PATZ1-induced CCNG2 transcription

[Display omitted] Cyclin G2 (CCNG2), a known inhibitor of cell cycle progression, has been identified as a suppressor for the canonical β-catenin pathway. This study explores the impact of CCNG2 on β-catenin activity and malignant characteristics of esophageal squamous cell carcinoma (ESCC) cells, and the mechanism behind CCNG2 dysregulation. In ESCC tissues and cells, CCNG2 was under-expressed and associated with poor clinical outcomes, whereas β-catenin showed an opposite trend. Inducing CCNG2 overexpression in ESCC cells led to a reduction in β-catenin levels, which in turn suppressed proliferation, cell cycle progression, migration, invasion, stemness, and tumorigenesis. Additionally, it enhanced the cytotoxicity and proliferation of T cells in co-culture systems. However, these beneficial effects were negated by the Wnt signaling agonist BML-284. Furthermore, PATZ1 was found as a transcription factor promoting CCNG2 transcription. However, the PATZ1 protein in ESCC cells was degraded by SMURF1. Silencing of SMURF1 restored CCNG2 expression and inhibited β-catenin, thereby suppressing the malignant phenotype of ESCC cells and reducing T cell exhaustion. Yet, these effects were blocked by further silencing of PATZ1. In summary, this research demonstrates that SMURF1 activates β-catenin signaling by suppressing the PATZ1/CCNG2 axis, thereby promoting the progression of ESCC.