Abstract 3543: USP7 inhibitor P5091 inhibits esophageal squamous cell carcinoma growth by inducing NOXA-mediated apoptosis

Abstract

Abstract Recently, deubiquitinase USP7/HAUSP was reported to be an attractive anti-cancer target. However, its expression and role in esophageal cancer remain elusive. Here, immunohistochemistry and western blot assay were used to detect the expression of USP7/HAUSP in esophageal squamous cell carcinoma (ESCC) tissues. Specific inhibitor P5091 was used to inhibit the activity of USP7 and explore the role and mechanism of USP7 in KYSE450, KYSE510 and KYSE30 ESCC cell lines. Result: Staining-intensity analysis by immunohistochemistry demonstrated that USP7 was expressed higher in ESCC tissues compared with their corresponding adjacent tissues (P<0.01), which was confirmed by western blot analysis. CCK-8 assay, colony formation assay and tumor growth assay in subcutaneous transplantation tumor model indicated that P5091 could significantly inhibit ESCC cell growth in vitro and in vivo. Moreover, P5091 induced apoptosis by triggering unfolded protein reaction, accumulating the protein of ATF4 and thus transcriptionally upregulating the expression of NOXA. Conclusion: These results showed that P5091 effectively inhibited ESCC cell growth in vitro and in vivo and supported the clinical investigation of P5091 for the treatment of ESCC. Keywords: P5091, esophageal squamous cell carcinoma, ATF4, apoptosis, NOXA * T H and J-Y Z contributed to this work equally. Citation Format: Tao Hu, Jing-Yang Zhang, Bei-Bei Sha, Miao-Miao Li, Xing-Ge Liu, Yi Zhang, Zi-Ming Dong, Pei Li, Ping Chen. USP7 inhibitor P5091 inhibits esophageal squamous cell carcinoma growth by inducing NOXA-mediated apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3543.