Abstract PO-021: Cell identity determines TCA cycle dynamics
| Autor: | Lydia W.S. Finley, Esther Drill, Paige K. Arnold, Benjamin T. Jackson, Lucas B. Sullivan, Sydney P. Alibeckoff |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Research. 80:PO-021 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.epimetab20-po-021 |
| Popis: | Cells utilize diverse metabolic strategies to support cell type-specific bioenergetic requirements. The enzymes that mediate cellular metabolic processes have been well studied. However, how cells coordinate these factors into metabolic networks remains poorly understood. Here we use measurements of gene dependency across hundreds of cancer cell lines to cluster metabolic genes into co-dependent modules. These analyses identified two distinct tricarboxylic acid (TCA) cycle modules with specific genetic dependencies. Isotope tracing combined with genetic manipulation of TCA cycle modules revealed that both normal stem cells and cancer cells can engage two different modes of TCA cycle metabolism. Enforcing self-renewal or differentiation induced preferential use of one TCA cycle module over another, indicating that TCA cycle dynamics are determined by cell state. In turn, the mode of TCA cycle metabolism employed by cells dictated nutrient dependencies, enabling cell-type specific responses to nutrient deprivation. Collectively, these studies reveal that TCA cycle behavior is dynamic and can be rerouted to confer a selective advantage to cells under different nutrient conditions. Citation Format: Paige K. Arnold, Benjamin T. Jackson, Sydney Alibeckoff, Esther Drill, Lucas B. Sullivan, Lydia W.S. Finley. Cell identity determines TCA cycle dynamics [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-021. |
| Databáze: | OpenAIRE |
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