Related Experiment Video
Updated: Feb 16, 2026
Absolute Quantification of Cell-Free Protein Synthesis Metabolism by Reversed-Phase Liquid Chromatography-Mass Spectrometry
Published on: October 25, 2019
Serine-Dependent Sphingolipid Synthesis Is a Metabolic Liability of Aneuploid Cells
Sunyoung Hwang1, H Tobias Gustafsson1, Ciara O'Sullivan1
1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
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.
Insights
Aneuploidy, an abnormal chromosome number, increases sphingolipids like ceramides. Targeting serine and sphingolipid synthesis may offer a novel strategy to impair aneuploid cancer cells.
Area of Science:
- Cell Biology
- Biochemistry
- Genetics
Background:
- Aneuploidy, an abnormal chromosome number, disrupts cellular balance but its underlying molecular mechanisms remain unclear.
- Aneuploidy is linked to diseases such as cancer and intellectual disability.
- Altered sphingolipid levels are observed in tumors and aneuploid cells, but their role in aneuploidy is unknown.
Purpose of the Study:
- To investigate the role of sphingolipids in cellular responses to aneuploidy.
- To explore the link between sphingolipid synthesis and serine metabolism in aneuploid cells.
- To assess the therapeutic potential of targeting sphingolipid and serine synthesis in aneuploid cells.
Main Methods:
- Analysis of sphingolipid levels in aneuploid cells.
- Genetic manipulation to alter ceramide levels.
- Inhibition of serine and sphingolipid synthesis pathways.
Main Results:
- Aneuploidy leads to increased levels of ceramides and long-chain bases, sphingolipids that inhibit proliferation and promote survival.
- Sphingolipid synthesis is closely connected to serine synthesis.
- Inhibiting serine or sphingolipid synthesis specifically impairs the fitness of aneuploid cells.
- Modulating ceramide levels genetically affects aneuploid cell fitness.
Conclusions:
- Sphingolipids play a crucial role in cellular adaptation to aneuploidy.
- The interplay between serine and sphingolipid synthesis is vital for aneuploid cell survival.
- Combined targeting of serine and sphingolipid synthesis presents a promising strategy for selectively eliminating aneuploid cancer cells.
Related Concept Videos
00:52What is Metabolism?
01:15Dehydration Synthesis
Dehydration synthesis (also called a condensation reaction) is the chemical process in which two molecules covalently link together to form a new molecule, along with the release of a water molecule. Many physiologically important compounds form by dehydration synthesis reactions, such as complex carbohydrates, proteins, DNA, and RNA.
Synthesis of carbohydrates
Sugar molecules are covalently linked together by dehydration synthesis. During the reaction, the hydroxyl (-OH) group from...
01:21Frequency-dependent Selection
02:17Synthesis and Decomposition Reactions
01:19Contact-dependent Signaling
Gap Junctions
In animal cells, gap junctions are formed...
01:59Lagging Strand Synthesis
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...