Mechanism dissection using ChIP and luciferase assays found that TR4 transcriptionally regulates the oncogene EZH2. EZH2 may then regulate the expression of its downstream key metastasis-related genes including NOTCH1, TGFβ1, SLUG, and MMP9. Adding back EZH2 in the TR4–shRNA PCa cell lines can partially interrupt the TR4–shRNA suppression effect on PCa cells invasion. Here, MMP9 is linked to posterior cortical atrophy.