Sphingosine-1-phosphate (S1P), together with other phosphosphingolipids, has been found to regulate complex cellular function in the tumor microenvironment (TME) where it acts as a signaling molecule that participates in cell-cell communication. S1P, through intracellular and extracellular signaling, was found to promote tumor growth, angiogenesis, chemoresistance, and metastasis; it also regulates anticancer immune response, modulates inflammation, and promotes angiogenesis. Interestingly, cancer cells are capable of releasing S1P and thus modifying the behavior of the TME components in a way that contributes to tumor growth and progression. Therefore, S1P is considered an important therapeutic target, and several anticancer therapies targeting S1P signaling are being developed and tested in clinics.
Keywords: Cancer metastasis; Cell motility; Chemotaxis; Hypoxia-inducible factor 1α (HIF1α); Immunomodulation; Inflammation; Macrophage polarization; Nuclear factor-κB (NF-κB); Sphingosine kinase (SphK); Sphingosine-1 phosphate (S1P); Sphingosine-1 phosphate receptors (S1PR); TAM/M2 macrophages; Tumor angiogenesis; Tumor growth; Tumor microenvironment.