Journal
ONCOTARGET
Volume 7, Issue 46, Pages 74427-74434Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12769
Keywords
degradome; CSCs; ubiquitin-specific proteases; gene targeting
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Funding
- Ministerio de Economia y Competitividad
- Instituto de Salud Carlos III (RTICC)
- Principado de Asturias, Spain
- Fundacion Bancaria Caja de Ahorros de Asturias
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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.
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