Extracellular and intracellular sphingosine-1-phosphate in cancer

Sphingosine-1-phosphate (S1P) was first described as a signaling molecule over 20 years ago. Since then, great strides have been made to reveal its vital roles in vastly different cellular and disease processes. Initially, S1P was considered nothing more than the terminal point of sphingolipid metabolism; however, over the past two decades, a large number of reports have helped unveil its full potential as an important regulatory, bioactive sphingolipid metabolite. S1P has a plethora of physiological functions, due in part to its many sites of actions and its different pools, which are both intra- and extracellular. S1P plays pivotal roles in many physiological processes, including the regulation of cell growth, migration, autophagy, angiogenesis, and survival, and thus, not surprisingly, S1P has been linked to cancer. In this review, we will summarize the vast body of knowledge, highlighting the connection between S1P and cancer. We will also suggest new avenues for future research.