Figure 1.

Role of sphingosine‐1‐phosphate (S1P) in cancer progression and inflammation. S1P is released into tumor microenvironment, where it promotes the invasion and migration of cancer cells, lymphangiogenesis, and recruitment of inflammatory cells. Cancer cells in the lymphatic vessels are stimulated by S1P, which promotes lymphatic spread of cancer. The figure below shows an enlarged view of the part surrounded by a red square, in which “Inside‐out signaling” process of S1P in tumor microenvironment is shown. S1P is generated from sphingosine (Sph) by sphingosine kinases 1 (SphK1) in the cytosol close to the plasma membrane in a cancer cell, and exported out of the cells via S1P transporters, such as ATP‐binding cassette (ABC) transporters or spinster 2 (Spns2) outside of cells. S1P stimulates specific S1P receptors (S1PR) to promote numerous cellular functions, such as cell proliferation, migration, angiogenesis and lymphangiogenesis, and recruitment of inflammatory cells by autocrine and/or paracrine manner