Importantly, our results showed that high levels of MDMX and MDM2 promoted a metastatic phenotype that correlated with increased CTCs and tumors expressing increased levels of CXCR4 and PTGS2. We found that MDMX had a strong influence on promoting CTCs, and upregulating CXCR4 and PTGS2. The fact that both CXCR4 and PTGS2 have been identified as key mediators of breast cancer metastasis to bone and lung [21, 22] provides a potential new combination targeting approach coupling MDM2, MDMX, CXCR4, and PTGS2 inhibition for a mechanism to block breast cancer metastasis. This evidence concerns the gene PTGS2 and breast cancer.