USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth

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	USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth
	An T 1,3; Gong YX 1,3; Gong L 1,3; Zhu HF 1,3; Yu CL 1,3; Liu JM 1,3; Zhou HY 1; Mao BY 2; Li X 1,3; Li Y[*]1
刊名	Biochemical Pharmacology
	2017
卷号	131 期号:X 页码:29-39
关键词	Colorectal cancer USP7 inhibitor Wnt signaling
通讯作者	liyanb@mail.kib.ac.cn
英文摘要	Aberrant activation of Wnt/β-catenin signaling is closely associated with the development of various human cancers, especially colorectal cancers (CRC). The ubiquitin proteasome system (UPS) is essential in the regulation of Wnt signaling and inhibitors targeting the UPS could have great potential in CRC therapy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, plays a significant role in neoplastic diseases due to its well-known function of regulating the MDM2-p53 complex. Inspired by our recent study identifying the positive role of USP7 in the Wnt signaling, we report here that USP7 is overexpressed in colorectal carcinoma cell lines and tissues, which is closely related with the poor prognosis. USP7 knockdown inhibits the proliferation of CRC cells with different p53 status, and USP7 inhibition by its inhibitor P5091 attenuates the activity of Wnt signaling via enhanced ubiquitination and the subsequent degradation of β-catenin. In vitro, P5091 inhibited the proliferation and induced apoptosis of CRC cells. P5091 also suppressed in vivo tumor growth in the HCT116 xenograft mouse model, which is consistently associated with reduced expression of β-catenin and Wnt target genes. In conclusion, our preclinical study indicated that USP7 could be a potential drug target and its inhibitor P5091 deserves further development as anticancer agent for Wnt hyper-activated CRC therapy.
收录类别	SCI
资助信息	This work was supported financially by the project of science and technology of Yunnan Province (2013FA047) and the open project of State Key Laboratory of Genetic Resources and Evo- lution (GREKF14-10).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/10895]
专题	昆明动物研究所_发育生物学昆明动物研究所_遗传资源与进化国家重点实验室
作者单位	1.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China 2.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 3.University of Chinese Academy of Sciences, Beijing, China
推荐引用方式 GB/T 7714	An T,Gong YX,Gong L,et al. USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth[J]. Biochemical Pharmacology,2017,131(X):29-39.
APA	An T.,Gong YX.,Gong L.,Zhu HF.,Yu CL.,...&Ma PC.(2017).USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth.Biochemical Pharmacology,131(X),29-39.
MLA	An T,et al."USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth".Biochemical Pharmacology 131.X(2017):29-39.