MT1-MMP regulates tumor progression via processing of bioactive proteins and extracellular matrices on the cell periphery, as well as through activation of hypoxia-inducible transcription factors in a cytoplasmic tail-mediated manner.12, 13, 14 The expression of both EphA2 and MT1-MMP is upregulated by the Ras/mitogen-activated protein kinase (MAPK) pathway and is frequently observed on cancer cell membranes.15, 16 EphA2 is an MT1-MMP substrate. This evidence concerns the gene EPHA2 and cancer.