2015 Fiscal Year Final Research Report
Comprehensive screening of glycolysis-related genes by synthetic lethality
| Project/Area Number |
24591313
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Keywords | がん / 解糖系 / スクリーニング / ユビキチンリガーゼ |
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| Outline of Final Research Achievements |
Glycolysis is a vital metabolic system. However, our understanding on glycolysis remains limited. To identify new genes involved in glycolysis regulation, we have performed a genome-wide gene knockdown analysis in human lung carcinoma PC8 cells using a mitochondrial inhibitor oligomycin and an shRNA library carried by a lentiviral vector, and finally identified five genes. Among them, we further focused on RNF126. RNF126 was found to act as a ubiquitin ligase for PDKs, resulting in their proteasomal degradation. This decrease in PDK levels allowed pyruvate dehydrogenases to catalyze the conversion of pyruvate to acetyl CoA. Moreover, depletion of RNF126 in cancer cells suppressed colony formation in soft agar as well as tumorigenicity in mice. RNF126 expression was found to be under the control of the ERK signaling pathway, which is essential for anoikis resistance. Thus, RNF126 is an attractive molecule for treating cancer by selectively targeting anchorage-independent growth.
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| Free Research Field |
分子腫瘍学
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