MAPK3 and cancer: Meanwhile, it is found that conjugated bile acids can activate the sphingosine 1-phosphate receptor 2 that activates intracellular ERK1/2 and AKT signaling to promote the invasive growth of cholangiocarcinoma, which is commonly associated with chronic cholestasis [33], and overexpression of bile acids in urine might result in worse condition of urinary bladder, even cancer.