Abstract
In contrast to terminally differentiated cells, cancer cells and stem cells retain the ability to re-enter the cell cycle and proliferate. To proliferate, cells must increase their uptake and catabolism of nutrients to support anabolic cell growth. Intermediates of central metabolic pathways have emerged as key players that influence cell-differentiation ‘decisions’, processes relevant to both oncogenesis and normal development. Consequently, how cells rewire metabolic pathways to support proliferation can have profound consequences for cellular identity. Here, we discuss the metabolic programs that support proliferation, and we explore how metabolic states are intimately entwined with the cell-fate decisions that characterize stem cells and cancer cells. By comparing the metabolism of pluripotent stem cells and cancer cells, we hope to illuminate common metabolic strategies as well as distinct metabolic features that may represent specialized adaptations to unique cellular demands.
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Acknowledgements
We thank members of the laboratories of A.M.I. and L.W.S.F. for discussion and J. Schvartzman and S. Vardhana for critical reading of the manuscript. A.M.I. is supported by the NIH/NCI (K08 CA201483), Damon Runyon Cancer Research Foundation (CI 95-18), Burroughs Wellcome Fund (CAMS 1015584), Leukemia & Lymphoma Society (SCOR 7011-16), Susan & Peter Solomon Divisional Genomics Program, Steven A. Greenberg Fund and Cycle for Survival. L.W.S.F. is supported as a Dale F. Frey-William Raveis Charitable Fund Scientist by the Damon Runyon Cancer Research Foundation (DFS-23-17). This work was additionally supported by the Searle Scholars program (to L.W.S.F.), The Starr Foundation (I11-0039 to L.W.S.F.) and Memorial Sloan Kettering Cancer Center Support Grant P30 CA008748.
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Intlekofer, A.M., Finley, L.W.S. Metabolic signatures of cancer cells and stem cells. Nat Metab 1, 177–188 (2019). https://doi.org/10.1038/s42255-019-0032-0
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DOI: https://doi.org/10.1038/s42255-019-0032-0
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