EGFR and cancer: Interestingly, “criss-cross” pathway activations often occur when bindings of S1P to S1PRs stimulate the receptor tyrosine kinases (RTKs) involved in the cancer proliferation and angiogenesis, for instance vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor (PDGFR), and at the same time the growth factors involved in these RTK activations can also enhance SPHK1 activity (Geffken and Spiegel, 2018).