The role of PPM1D in cancer and advances in studies of its inhibitors

被引:39
作者
Deng, Wenhong [1 ,2 ,3 ]
Li, Jieqing [2 ,3 ]
Dorrah, Kimberly [2 ,3 ]
Jimenez-Tapia, Denise [2 ,3 ]
Arriaga, Brando [2 ,3 ]
Hao, Qiongyu [2 ,3 ]
Cao, Wei [2 ,3 ]
Gao, Zhaoxia [4 ,5 ]
Vadgama, Jay [2 ,3 ]
Wu, Yong [2 ,3 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Gen Surg, Wuhan 430060, Peoples R China
[2] Charles Drew Univ Med & Sci, David Geffen UCLA Sch Med, Dept Internal Med, Div Canc Res & Training, Los Angeles, CA USA
[3] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA
[4] 5th Hosp Wuhan, Dept Gen Surg, Wuhan 430050, Peoples R China
[5] Johns Hopkins Univ Hosp, Dept Surg, Bayview Campus, Baltimore, MD 21287 USA
基金
中国国家自然科学基金; 美国国家卫生研究院;
关键词
PPM1D; Phosphatase; Inhibitor; p53; Cancer; PHOSPHATASE; 1; WIP1; PROTEIN PHOSPHATASE; BREAST-CANCER; CLINICAL-SIGNIFICANCE; CLONAL HEMATOPOIESIS; IONIZING-RADIATION; CHEMICAL INHIBITOR; CARCINOMA-CELLS; POOR-PROGNOSIS; EXPRESSION;
D O I
10.1016/j.biopha.2020.109956
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
A greater understanding of factors causing cancer initiation, progression and evolution is of paramount importance. Among them, the serine/threonine phosphatase PPM1D, also referred to as wild-type p53-induced phosphatase 1 (Wip1) or protein phosphatase 2C delta (PP2Cd), is emerging as an important oncoprotein due to its negative regulation on a number of crucial cancer suppressor pathways. Initially identified as a p53-regulated gene, PPM1D has been afterwards found amplified and more recently mutated in many human cancers such as breast cancer. The latest progress in this field further reveals that selective inhibition of PPM1D to delay tumor onset or reduce tumor burden represents a promising anti-cancer strategy. Here, we review the advances in the studies of the PPM1D activity and its relevance to various cancers, and recent progress in development of PPM1D inhibitors and discuss their potential application in cancer therapy. Consecutive research on PPM1D and its relationship with cancer is essential, as it ultimately contributes to the etiology and treatment of cancer.
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页数:10
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