USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation

被引：83

作者：

Hou, Pingping ^{[1
]}

Ma, Xingdi ^{[1
]}

Zhang, Qiang ^{[1
]}

Wu, Chang-Jiun ^{[2
]}

Liao, Wenting ^{[1
,3
]}

Li, Jun ^{[2
]}

Wang, Huamin ^{[4
,5
]}

Zhao, Jun ^{[5
]}

Zhou, Xin ^{[1
]}

Guan, Carolyn ^{[6
]}

Ackroyd, Jeffery ^{[7
]}

Jiang, Shan ^{[8
]}

Zhang, Jianhua ^{[2
]}

Spring, Denise J. ^{[1
]}

Wang, Y. Alan ^{[1
]}

DePinho, Ronald A. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77054 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA

[3] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China

[4] Univ Texas MD Anderson Canc Ctr, Dept Anat Pathol, Houston, TX 77054 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77054 USA

[6] Princeton Univ, Princeton, NJ 08544 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Canc Syst Imaging, Houston, TX 77054 USA

[8] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77054 USA

来源：

GENES & DEVELOPMENT | 2019年 / 33卷 / 19-20期

基金：

美国国家卫生研究院;

关键词：

pancreatic cancer; TCF7; USP21; Wnt pathway; cancer stemness; deubiquitinase; CROSS-TALK; UBIQUITINATION; SUBTYPES; GENES;

D O I：

10.1101/gad.326314.119

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates murine PDAC tumor growth and drives PanIN to PDAC progression in immortalized human pancreatic ductal cells. Conversely, depletion of USP21 impairs PDAC tumor growth. Mechanistically, USP21 deubiquitinates and stabilizes the TCF/LEF transcription factor TCF7, which promotes cancer cell stemness. Our work identifies and validates USP21 as a PDAC oncogene, providing a potential drug-gable target for this intractable disease.

引用

页码：1361 / 1366

页数：6

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