Serine-Dependent Sphingolipid Synthesis Is a Metabolic Liability of Aneuploid Cells.
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| Abstract |
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.
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| Authors | Sunyoung Hwang, H Tobias Gustafsson, Ciara O'Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M Torres |
| Journal | Cell reports (Cell Rep) Vol. 21 Issue 13 Pg. 3807-3818 (12 26 2017) ISSN: 2211-1247 [Electronic] United States |
| PMID | 29281829 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved. |
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