Differential Aspartate Usage Identifies a Subset of Cancer Cells Particularly Dependent on OGDH.
Cell Reports(2016)
Agios Pharmaceut
Abstract
Although aberrant metabolism in tumors has been well described, the identification of cancer subsets with particular metabolic vulnerabilities has remained challenging. Here, we conducted an siRNA screen focusing on enzymes involved in the tricarboxylic acid (TCA) cycle and uncovered a striking range of cancer cell dependencies on OGDH, the E1 subunit of the alpha-ketoglutarate dehydrogenase complex. Using an integrative metabolomics approach, we identified differential aspartate utilization, via the malate-aspartate shuttle, as a predictor of whether OGDH is required for proliferation in 3D culture assays and for the growth of xenograft tumors. These findings highlight an anaplerotic role of aspartate and, more broadly, suggest that differential nutrient utilization patterns can identify subsets of cancers with distinct metabolic dependencies for potential pharmacological intervention.
MoreTranslated text
Key words
alpha-ketoglutarate dehydrogenase,oxoglutarate dehydrogenase,OGDH,citric acid cycle,TCA cycle,Krebs cycle,malate-aspartate shuttle,aspartate,cancer metabolism,target validation
PDF
View via Publisher
AI Read Science
Must-Reading Tree
Example

Generate MRT to find the research sequence of this paper
Data Disclaimer
The page data are from open Internet sources, cooperative publishers and automatic analysis results through AI technology. We do not make any commitments and guarantees for the validity, accuracy, correctness, reliability, completeness and timeliness of the page data. If you have any questions, please contact us by email: report@aminer.cn
Chat Paper
Summary is being generated by the instructions you defined