Because of the effect of MAPK on the expressions of DNMT1, HDAC2, and p16 induced by PAR4-AP, it is likely that the inhibitions of DNMT1 and HDAC2 induced by PAR4 activation are involved in the expression of p16 via MAPK signals in ESCC cells. Here, F2RL3 is linked to esophageal squamous cell carcinoma.