Hypoxia induces epithelial-mesenchymal transition in colorectal cancer cells through ubiquitin-specific protease 47-mediated stabilization of Snail: A potential role of Sox9.
Sci Rep
; 7(1): 15918, 2017 Nov 21.
Article
en En
| MEDLINE
| ID: mdl-29162839
ABSTRACT
During the metastatic phase, cancer cells require the dissolution of cadherin-mediated cell-cell adhesion and a dramatic re-organization of the cytoskeleton through epithelial-mesenchymal transition (EMT), thereby acquiring migratory and invasive capabilities. In most tumors, EMT is accompanied by hypoxia. However, the intracellular signaling molecule that mediates hypoxia-induced EMT remained overlooked. By utilizing the microarray database system of the Cancer Genome Atlas, we identified ubiquitin-specific protease 47 (USP47), a deubiquitinating enzyme, as a potential mediator of hypoxia-induced EMT. Immunofluorescence staining of human colorectal tissue microarrays revealed that USP47 is overexpressed in colorectal adenocarcinoma tissues compared with normal adjacent tissues. The expression of USP47 was found to be elevated in three different human colorectal cancer cell lines. The enhancement of USP47 in colorectal cancer cells under hypoxic conditions induced the disassembly of E-cadherin and promoted EMT through deubiquitination of Snail. Silencing of USP47 accelerated the proteasomal degradation of Snail and inhibited EMT. Notably, hypoxia-induced USP47 upregulation was mediated by Sox9. These results demonstrate, for the first time, the role for USP47, as a novel target of Sox9, in the regulation of EMT and metastasis of colorectal cancer cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Ubiquitina Tiolesterasa
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Factor de Transcripción SOX9
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Transición Epitelial-Mesenquimal
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Factores de Transcripción de la Familia Snail
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article