The deubiquitinase USP54 is overexpressed in colorectal cancer stem cells and promotes intestinal tumorigenesis

被引：27

作者：

Fraile, Julia M. ^{[1
]}

Campos-Iglesias, Diana ^{[1
]}

Rodriguez, Francisco ^{[1
]}

Espanol, Yaiza ^{[1
]}

Freije, Jose M. P. ^{[1
]}

机构：

[1] Univ Oviedo, Inst Univ Oncol, Fac Med, Dept Bioquim & Biol Mol, Oviedo, Spain

来源：

ONCOTARGET | 2016年 / 7卷 / 46期

关键词：

degradome; CSCs; ubiquitin-specific proteases; gene targeting; PROTEASES; RELAPSE; DISEASE; SYSTEM; ROLES;

D O I：

10.18632/oncotarget.12769

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis. In agreement with these results, Usp54 downregulation in mouse melanoma cells inhibits lung metastasis formation. Collectively, this work has uncovered the pro-tumorigenic properties of USP54, highlighting the importance of deubiquitinating enzymes as promising targets for the development of specific anti-cancer therapies.

引用

页码：74427 / 74434

页数：8

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