Fig. 8.

Schematic diagram about the molecular mechanism of melatonin inhibiting ESCC cell growth. ① USP10 deubiquitinates and stabilizes HDAC7 protein in the ESCC cells. Moreover, melatonin downregulates HDAC7 by both decreasing HDAC7 transcription and reducing protein stability through USP10 inhibition. ② HDAC7 physically deacetylates β-catenin Lys49, thus hindering β-catenin phosphorylation and subsequently activating target c-Myc gene expression. Interestingly, HDAC7/β-catenin/c-Myc could form a positive feedback loop to enhance ESCC cell growth, and melatonin works as a potent HDAC7 inhibitor thus prohibiting ESCC proliferation. USP10 ubiquitin-specific protease 10, HDAC7 histone deacetylase 7, ESCC esophageal squamous cell carcinoma