title: The deubiquitinase USP54 is overexpressed in colorectal cancer stem cells and promotes intestinal tumorigenesis.
abstract: 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.
authors: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
authors: Julia M
authors: JM
authors: Fraile
authors: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
authors: Diana
authors: D
authors: Campos-Iglesias
authors: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
authors: Francisco
authors: F
authors: Rodríguez
authors: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
authors: Yaiza
authors: Y
authors: Español
authors: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
authors: José M P
authors: JM
authors: Freije
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D047108:Embryonic Development / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C579191:USP54 protein, human; D064570:Ubiquitin-Specific Proteases
keywords: CSCs; degradome; gene targeting; ubiquitin-specific proteases