UMass Metabolic Network; Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Genetics and Genomics | Molecular Biology
Aneuploidy disrupts cellular homeostasis. However, the molecular mechanisms underlying the physiological responses and adaptation to aneuploidy are not well understood. Deciphering these mechanisms is important because aneuploidy is associated with diseases, including intellectual disability and cancer. Although tumors and mammalian aneuploid cells, including several cancer cell lines, show altered levels of sphingolipids, the role of sphingolipids in aneuploidy remains unknown. Here, we show that ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy. Sphingolipid levels are tightly linked to serine synthesis, and inhibiting either serine or sphingolipid synthesis can specifically impair the fitness of aneuploid cells. Remarkably, the fitness of aneuploid cells improves or deteriorates upon genetically decreasing or increasing ceramides, respectively. Combined targeting of serine and sphingolipid synthesis could be exploited to specifically target cancer cells, the vast majority of which are aneuploid.
aneuploidy, ceramide, chromosomes, genomic istability, long-chain bases, metabolism, myriocin, serine, sphingolipids, sphingosine
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Copyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Cell Rep. 2017 Dec 26;21(13):3807-3818. doi: 10.1016/j.celrep.2017.11.103. Link to article on publisher's site
Hwang, Sunyoung; Gustafsson, H. Tobias; O'Sullivan, Ciara; Bisceglia, Gianna; Huang, Xinhe; Klose, Christian; Schevchenko, Andrej; Dickson, Robert C.; Cavaliere, Paola; Dephoure, Noah; and Torres, Eduardo M., "Serine-Dependent Sphingolipid Synthesis Is a Metabolic Liability of Aneuploid Cells" (2017). University of Massachusetts Medical School Faculty Publications. 1472.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.