PKM2 interacted with ERK1/2 and regulated ERK1/2 activity, leading to the phosphorylation of c-Jun, not c-Fos, initiating transactivation of COX-2, and promoting cell invasion/EMT, while inhibition of COX-2 reversed the promotion of PKM2 on tumor invasion/EMT in vivo and in vitro. Here, MAPK3 is linked to neoplasm.