STAT3 and cholangiocarcinoma: The link between S1P and STAT3 is not restricted to S1PR1; thus, pharmacological inhibition of SphK2 abrogated STAT3 phosphorylation, leading to decreased proliferation of cholangiocarcinoma cells (160), while in ER-negative breast cancer cells, SphK1 knockdown led to a significant reduction in leptin-induced STAT3 phosphorylation (161).