Immunohistochemical analysis of several cancer tissues revealed that EphA2 coexpressed with MT1-MMP in several carcinoma tissues mostly lacked the N-terminal ligand-binding domain, and activated ligand-independent EphA2 signaling (phosphorylation of Ser897).5, 9 Forced expression of an uncleavable EphA2 mutant in carcinoma cells altered cell morphology to epithelial-like forms, and suppressed tumor growth and lung metastasis in mice. This evidence concerns the gene EPHA2 and cancer.