S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Theses (Master's Degree_분자의학 및 바이오제약학과)
Functional Implications of Leucyl-tRNA Synthetase in Colorectal Cancer
- 융합과학기술대학원 분자의학 및 바이오제약학과
- Issue Date
- 서울대학교 융합과학기술대학원
- 학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과 의약생명과학 전공, 2016. 2. 김성훈.
- Colorectal cancer is one of challenging cancers that has high incidence rate and death rate at the same time . 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.