Abstract: Objective To study the role of proline-rich tyrosine kinase 2(PYK-2) in the invasion and migration of Human Colorectal Cancer SW480 Cells induced by PGE2. Methods The cells were divided into A、B、C and D group,including control group,PGE2 group, PGE2+SC19220(the antagonist of EP1)group and PGE2+BAPTA-AM(Ca2+ chelator)group.The mRNA levels of the four types of EP receptors(EP1,EP2,EP3,EP4) of PGE2 in SW480 were analyzed by RT-PCR. Western blotting was used to detect the protein level of PYK-2,the invasive and migrative ability of SW480 cells was examined by transwell assay. Results EP1,EP2 and EP4 expressed in SW480 cells, and the mRNA level of EP1 elevated after being treated with PGE2. The phosphorylation level of PYK-2 increased gradually within ten minutes after the treatment of PGE2, and the statistically significant differences were observed among the PYK-2 phosphorylation at different time points including 0 min,5 min and 10 min (P<0.05), and there was no difference between the level at 30 and 0 min(P>0.05); the PYK-2 phosphorylation of C group and D group degraded,compared with that of B group (P<0.05), the ability of invasion and migration of SW480 cells degraded accordingly(P<0.05). Conclusion PGE2 may promote the phosphorylation of PYK-2 via Ca2+ and EP1,then induce the invasion and migration of human colorectal cancer cells.