Epigenetic Regulation Mediated by Sphingolipids in Cancer

Epigenetic changes are heritable modifications that do not directly affect the DNA sequence. In cancer cells, the maintenance of a stable epigenetic profile can be crucial to support survival and proliferation, and said profile can differ significantly from that of healthy cells. The epigenetic profile of a cancer cell can be modulated by several factors, including metabolites. Recently, sphingolipids have emerged as novel modulators of epigenetic changes. Ceramide and sphingosine 1-phosphate have become well known in cancer due to activating anti-tumour and pro-tumour signalling pathways, respectively, and they have recently been shown to also induce several epigenetic modifications connected to cancer growth. Additionally, acellular factors in the tumour microenvironment, such as hypoxia and acidosis, are now recognised as crucial in promoting aggressiveness through several mechanisms, including epigenetic modifications. Here, we review the existing literature on sphingolipids, cancer, and epigenetic changes, with a focus on the interaction between these elements and components of the chemical tumour microenvironment.

Automated summary

Epigenetic changes, which are heritable modifications not affecting DNA sequence directly, are crucial for the survival and proliferation of cancer cells, as they can differ significantly from healthy cells. Recently, sphingolipids have been identified as novel modulators of epigenetic changes in cancer, with ceramide and sphingosine 1-phosphate inducing various epigenetic modifications linked to cancer growth. Moreover, acellular factors in the tumor microenvironment, such as hypoxia and acidosis, play a crucial role in promoting aggressiveness through epigenetic modifications. This review focuses on the interaction between sphingolipids, cancer, epigenetic changes, and the chemical tumor microenvironment.