Meta-Biol

• Pathways

Estrogen stimulation of breast cancer cells promotes ESR1- dependent activation of sphingosine kinase 1 (SPHK1) (Sukocheva et al, 2003; Sukhocheva et al, 2006). SPHK1 catalyzes the formation of sphingosine-1-phosphate (S1P) , a ligand for the GPCR S1PR3 receptor, also known as EDG3 (Hla et al, 2001; Spiegel and Milstein, 2003; Sukocheva et al, 2006). S1P-bound S1PR3 stimulates EGFR transactivation downstream of estradiol stimulation through the MMP-dependent release of HBEGF from the plasma membrane, leading to EGFR and MAPK phosphorylation (Kim et al, 2000; Tanimoto et al, 2004; Filardo et al, 2000; Razandi et al, 2003; Sukocheva et al, 2003; Sukocheva et al, 2006; reviewed in Prossnitz and Barton, 2014).