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Role of Ubiquitin-specific Protease 47 in Hypoxia-induced Epithelial Mesenchymal Transition in Human Colorectal Cancer Cells : 저산소상태에 의해 유도된 대장암 세포의 상피간엽이행 촉진과정에서 USP47의 역할
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- Authors
- Advisor
- 서영준
- Major
- 약학대학 약학과
- Issue Date
- 2018-02
- Publisher
- 서울대학교 대학원
- Keywords
- USP47 ; Colorectal Cancer ; Hypoxia ; Epitheial Mesenchymal Transition ; Snail
- Description
- 학위논문 (박사)-- 서울대학교 대학원 : 약학대학 약학과, 2018. 2. 서영준.
- 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.
- Language
- English
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