The authors investigated the role of matrix metalloproteinase 3 (MMP3) in colorectal cancer (CRC) progression. They identified endothelial PAS domain protein 1 (EPAS1) as a key downstream target. This study included comprehensive validation of MMP3 overexpression in clinical CRC samples (TCGA datasets, paired tissues, tissue microarray), gain- and loss-of-function in vitro assays, and in vivo xenograft validation.