Differential Aspartate Usage Identifies a Subset of Cancer Cells Particularly Dependent on OGDH
Citations Over TimeTop 11% of 2016 papers
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.
Related Papers
- → Not just a circle: flux modes in the plant TCA cycle(2010)848 cited
- → Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle(2021)25 cited
- → Regulation of leukocyte tricarboxylic acid cycle in drug-naïve Bipolar Disorder(2015)12 cited
- → Regulation of the tricarboxylic acid cycle pool size in heart muscle(1984)55 cited
- → Metabolism related to the tricarboxylic aid cycle in rat brain slices. Observations on CO2 fixation and metabolic compartmentation(1972)30 cited