Sphingosine 1-phosphate signalling in cancer stem cells

Cancer stem cells (CSCs) are considered the head of a hierarchical organisation of carcinogenesis, exhibiting heightened cell survival properties, an ability to endlessly self-renew and undergo attenuated differentiation to maintain the bulk tumour population. The acquisition of cancer stem cell properties including dysregulated self-renewal and differentiation trajectories, is a dynamic disease-specific process underpinned by numerous genetic changes and signalling network aberrations. The bioactive sphingolipid, sphingosine 1-phosphate (S1P), has emerged as a key regulator of CSC biology. Historically, S1P has been associated with maintaining tissue homeostasis and immune responses, but recent studies have revealed that dysregulation of S1P-mediated cellular signalling plays important roles in CSC biology. This review provides an overview of the role of S1P in stem cell biology in both normal physiology and disease. It also describes approaches to target this signalling pathway, where aberrant, with the goal of eradicating the CSC population responsible for cancer initiation and progression, and importantly, patient relapse to many clinical therapeutics.