In this study, pharmacological inhibition of the integrin α2β1–FAK–JNK signaling axis effectively abolished PDA-induced adhesion, migration, invasion, proliferation, stemness- and EMT-associated gene expression, and chemoresistance, supporting the conclusion that PDA-enhanced malignant traits are dependent on integrin α2β1–FAK–JNK signaling. Here, PTK2 is linked to Patent ductus arteriosus.