It has been shown that sphingosine-1-phosphate receptor-1 (S1PR1) upregulates tyrosine–protein kinase JAK2 (JAK2) activity, increasing STAT3 phosphorylation in tumor cells, and STAT3 regulates S1PR1 and IL-6, resulting in a positive feedback loop [167,168]. Here, STAT3 is linked to neoplasm.