Industry News: New Approach to Kill Cancer via Sphingolipids

Researchers at Southwest Jiaotong University have identified serine and sphingolipid synthesis as the Achilles heel of aneuploid cancer cells

01 Feb 2018

Sphingolipid synthesis is vital for cellular signalling and integrity, yet research at Jiaotong University has shown that cancer cells with chromosomal defects produce an excess of sphingolipids that might drive pro-survival pathways. Results from the study also suggest that inhibition of sphingolipid synthesis is able to cause cancer cell death.

Cancer cells are the direct result of pro-survival genetic alterations that enable persistence and proliferation in the body. Whilst the majority of cells that acquire genetic disturbances are recognised and targeted for cell death, those that survive often develop into cancers. Aneuploidy is a term used to describe cells that have undergone chromosome mis-segregation, a deleterious event that results in the losing or gaining of a chromosome. This a common defect in tumour cells and may lead to the loss of tumour suppressor genes or duplication of oncogenes. However, little is known about the specific pathways that drive tumourigenicity in aneuploid cells.

In an article published by Cell Reports, a group from the School of Life Science and Engineering at Southwest Jiaotong University, China, have identified a dependency of aneuploid cells on increased de novo sphingolipid synthesis for survival. Furthermore, this was found to be common to all strains of yeast aneuploid cells. Sphingolipids are important membrane components that directly influence sub-cellular signalling, protein biosynthesis, RNA biosynthesis and metabolic pathways. By applying global lipidomic mass spectrometry (MS), and quantitative MS techniques by Lipotype, to a series of aneuploid yeast strains, the team have recognized an increase in the abundance of intermediates such as long chain bases (LCBs) and ceramides, that are primarily involved in sphingolipid synthesis.  

When compared to wild type cells, the team identified a striking dependency on serine, a long chain base, for sphingolipid synthesis and proliferation. Growth of cells decreased considerably when enzymes such as serine palmitoyl transferase and phosphoserine phosphatase, were inhibited. This provides the intriguing possibility that combined inhibition of sphingolipid and serine synthesis, might confer therapeutic sensitivity for these types of cancer cells.