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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
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 서영준 | - |
dc.contributor.author | 최배정 | - |
dc.date.accessioned | 2018-05-28T16:51:59Z | - |
dc.date.available | 2018-05-28T16:51:59Z | - |
dc.date.issued | 2018-02 | - |
dc.identifier.other | 000000151536 | - |
dc.identifier.uri | https://hdl.handle.net/10371/140954 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 약학대학 약학과, 2018. 2. 서영준. | - |
dc.description.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. | - |
dc.description.tableofcontents | Introduction 14
1. Role of ubiquitin in cellular processes 14 2. General properties of deubiquitinating enzymes (DUBs) 15 3. DUBs and cancer 25 4. Role of USP47 in hypoxia-induced EMT in human colorectal cancer cells 36 Materials and Methods 40 Results 51 Discussion 109 References 118 Abstract in Korean (국문 초록) 138 | - |
dc.format | application/pdf | - |
dc.format.extent | 2531844 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | USP47 | - |
dc.subject | Colorectal Cancer | - |
dc.subject | Hypoxia | - |
dc.subject | Epitheial Mesenchymal Transition | - |
dc.subject | Snail | - |
dc.subject.ddc | 615 | - |
dc.title | Role of Ubiquitin-specific Protease 47 in Hypoxia-induced Epithelial Mesenchymal Transition in Human Colorectal Cancer Cells | - |
dc.title.alternative | 저산소상태에 의해 유도된 대장암 세포의 상피간엽이행 촉진과정에서 USP47의 역할 | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.contributor.affiliation | 약학대학 약학과 | - |
dc.date.awarded | 2018-02 | - |
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