USP53 Inhibits Cell Proliferation and Glutamine Metabolism by Inactivating the β-Catenin Signaling via Deubiquitination of Axin1 in Esophageal Squamous Cell Carcinoma

Abstract

Background: Despite the overall decline in the incidence rate of esophageal squamous cell carcinoma (ESCC), it remains a high rate of mortality. As a deubiquitinating enzyme, the antitumor effect of ubiquitin-specific peptidase 53 (USP53) has been demonstrated on a few malignancies, but its role and mechanism in ESCC have not been clarified. Therefore, this study aims to explore the role and mechanism of USP53 in ESCC. Methods: The effects of USP53 combined with and without axis inhibition protein (Axin1) on cell functions were explored using the CCK-8 (Cell Counting Kit-8 assay) and Flow cytometry assay. The corresponding molecular mechanisms were further detected using Western blot assays. The combination of USP53 and Axin1 was verified by the immunoprecipitation assay. The influence of USP53 on the growth of implanted tumors was tested in vivo and the mechanism was further confirmed by western blot. Results: USP53 overexpression inhibited ESCC cell viability, cell cycle progression and glutamine metabolism in vitro, but inhibition of USP53 had the opposite effect. Similar results were also obtained in vivo showing that overexpression of USP53 suppressed tumor growth. In addition, we found that USP53 interacted with and induced deubiquitination of Axin1. Mechanistically, USP53 silencing promoted ESCC cell viability and cell cycle progression through the deubiquitination of Axin1. Conclusions: USP53 inhibits the development of ESCC by regulating the deubiquitination of Axin1. USP53 may be used as a molecular target for ESCC therapy.