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Functional Implications of Leucyl-tRNA Synthetase in Colorectal Cancer

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dc.contributor.advisor김성훈-
dc.contributor.author장자윤-
dc.date.accessioned2017-07-19T11:08:31Z-
dc.date.available2019-04-17-
dc.date.issued2016-02-
dc.identifier.other000000132314-
dc.identifier.urihttps://hdl.handle.net/10371/133388-
dc.description학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과 의약생명과학 전공, 2016. 2. 김성훈.-
dc.description.abstractColorectal cancer is one of challenging cancers that has high incidence rate and death rate at the same time [1]. However, since the effective targets and chemotherapeutic agents used in clinic are lack, it is necessary to identify the new drug target for controlling colorectal cancer.
Here we found that leucyl-tRNA synthetase (LRS), known as a leucine sensor of mTOR signaling, is highly expressed in colorectal cancer patient tissues as well as diverse colorectal cancer cell lines [2, 3]. LRS expression significantly promotes cancer cell growth and proliferation as determined by immunoblotting, immunohistochemistry, [35S] Met incorporation, anchorage independent growth, and xenograft assay. In addition, LRS expression is positively correlated with phosphorylation of S6Kinase which is a downstream effector of mTOR. Silencing of LRS attenuates the phosphorylation of S6K, oncogenic growth, tumor mass while increase of LRS expression enhances tumorigenic propensity. Therefore, the regulation of mTOR-S6kinase pathway via suppression of LRS expression is effective way to control cancer cell growth. Taken together, this is consistent with observation that LRS may be suggested as a potential therapeutic target to control colorectal cancer and that effective tools for LRS are needed further validation and study.
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dc.description.tableofcontentsI. INTRODUCTION 6

II. MATERIALS AND METHODS 8
1. Materials 8
2. Cell culture 8
3. Immunohistochemistry 9
4. Immunoblotting 10
5. Establishment of LRS shRNA, myc-LRS expression cell line 11
6. Leucine starvation and stimulation of cells 12
7. Methionine incorporation 12
8. Colony formation assay 13
9. Xenograft tumors 13

III. RESULTS 15
1. LRS is highly expressed in colorectal cancer 15
2. Increase of LRS enhances mTORC1 activity and tumor growth 16
3. LRS upregulation promotes tumorigenic transformation in xenograft model 17
4. Downregulation of LRS suppresses mTORC1 activity and tumor growth 17
5. LRS suppression inhibits tumorigenic transformation in xenograft model 18

IV. DISCUSSION 26

V. REFERENCES 28

VI. 국문초록 30
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dc.formatapplication/pdf-
dc.format.extent1053108 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 융합과학기술대학원-
dc.subjectLeucyl-tRNA synthetase-
dc.subjectmTOR-
dc.subjectcolorectal cancer-
dc.subjecttumorigenicity-
dc.subjecttherapeutic target-
dc.subject.ddc610-
dc.titleFunctional Implications of Leucyl-tRNA Synthetase in Colorectal Cancer-
dc.typeThesis-
dc.description.degreeMaster-
dc.citation.pages32-
dc.contributor.affiliation융합과학기술대학원 분자의학 및 바이오제약학과-
dc.date.awarded2016-02-
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Theses (Master's Degree_분자의학 및 바이오제약학과)
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