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USP10-mediated MOF (KAT8) stabilization accelerates the malignant progression of esophageal squamous cell carcinoma via epigenetically activating of ANXA2/Wnt signaling

ABSTRACT: Dysregulation of MOF (MYST1, KAT8), a highly conserved H4K16 acetyltransferase, plays important roles in human cancers. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we report that MOF is highly expressed in ESCC tumors and predicts a worse prognosis. Depletion of MOF in ESCC significantly impedes tumor growth and metastasis both in vitro and in vivo, whereas ectopic expression of MOF but not enzyme inactive mutant (MOF E350Q) promotes ESCC progression, suggesting that MOF acetyltransferase activity is crucial for its oncogenic activity. Further analysis reveals that USP10, a deubiquitinase highly expressed in ESCC, binds to and protects MOF from proteosome-dependent protein degradation. MOF stabilization by USP10 promotes H4K16ac enrichment in the ANXA2 promoter to stimulate ANXA2 transcription, which subsequently activates Wnt/ β-Catenin signaling to facilitate ESCC progression. Our findings highlight a novel USP10/MOF/ANXA2 axis as a promising therapeutic target for ESCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE241066 | GEO | 2024/01/09

REPOSITORIES: GEO

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