El-Kenawi et al., 2023 Persisters: the story of cells left behind!

Evolution of resistance is a major barrier to prolonged tumor control. Growing evidence suggests that resistance can be driven by few number of cells which remains after treatment, known as persisters or residual tumor cells. How these cells resist anti-cancer treatment? It depends on the way they die with or what we call “cell death pathways”!

There are many types of cell death pathway:  such as apoptosis, necroptosis, pyroptosis and necrosis.

In this paper, we focus on mechanism which enable resistance to pyroptosis, a type of inflammatory cell death which usually occur in macrophages, a type of innate immune cells. To decipher the molecular mechanisms of resistance to pyroptosis, we combined time-lapse imaging with longitudinal DNA/RNA sequencing and metabolomics. We found that these persisters lap up methionine to counteract the detrimental impact of pyroptosis signaling on plasma membrane integrity. However, this will also increase the methylation capacity leading to various epigenetic changes.

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