University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

UMass Metabolic Network; Department of Molecular, Cell and Cancer Biology

Publication Date

12-26-2017

Document Type

Article

Disciplines

Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Genetics and Genomics | Molecular Biology

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.

Keywords

aneuploidy, ceramide, chromosomes, genomic istability, long-chain bases, metabolism, myriocin, serine, sphingolipids, sphingosine

Rights and Permissions

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

10.1016/j.celrep.2017.11.103

Source

Cell Rep. 2017 Dec 26;21(13):3807-3818. doi: 10.1016/j.celrep.2017.11.103. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cell reports

PubMed ID

29281829

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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