The study investigates the molecular mechanisms by which matrix metalloproteinase-3 (MMP-3) induces epithelial-mesenchymal transition (EMT) and genomic instability in mouse mammary epithelial cells. MMP-3 exposure leads to the expression of an alternatively spliced form of Rac1, Rac1b, which increases cellular reactive oxygen species (ROS). These ROS stimulate the transcription factor Snail, leading to EMT and genomic instability. The findings reveal a novel pathway where components of the tumor microenvironment, specifically MMP-3, alter cellular structure in culture and tissue structure in vivo, promoting malignant transformation. The study also demonstrates that MMP-3-induced ROS cause DNA damage and genomic instability, as evidenced by increased 8-oxoguanosine staining and resistance to N-(phosphonacetyl)-L-aspartate (PALA). These results highlight the role of MMP-3 in promoting tumor progression and provide insights into the mechanisms underlying genomic instability in breast cancer.The study investigates the molecular mechanisms by which matrix metalloproteinase-3 (MMP-3) induces epithelial-mesenchymal transition (EMT) and genomic instability in mouse mammary epithelial cells. MMP-3 exposure leads to the expression of an alternatively spliced form of Rac1, Rac1b, which increases cellular reactive oxygen species (ROS). These ROS stimulate the transcription factor Snail, leading to EMT and genomic instability. The findings reveal a novel pathway where components of the tumor microenvironment, specifically MMP-3, alter cellular structure in culture and tissue structure in vivo, promoting malignant transformation. The study also demonstrates that MMP-3-induced ROS cause DNA damage and genomic instability, as evidenced by increased 8-oxoguanosine staining and resistance to N-(phosphonacetyl)-L-aspartate (PALA). These results highlight the role of MMP-3 in promoting tumor progression and provide insights into the mechanisms underlying genomic instability in breast cancer.