Downregulation of CXCR4 by E1A

5656 The adenovirus type 5 E1A proteins have multiple antitumor effects on tumor cells, including reversion of transformation, induction of apoptosis and inhibition of metastasis, which have been used in the clinical trial since 1995. Although the functionality of E1A as a tumor suppressor has been extensively studied, its role in inhibition of tumor progression is still not being completely understood, especially its role in inhibition of metastasis. Recently, it was suggested that CXCR4 is involved in the targeted metastasis of breast cancer to lung, of prostate cancer to the bone marrow and of colon cancer to the liver. Here we show that E1A can inhibit the CXCR4 expression by FACS analysis and immunofluorescent staining. Further more E1A inhibits invasive activity induced by CXCR4 in vitro. Finally we found that E1A can suppress CXCR4 transcriptional activity by inhibiting HIF regulation element on the CXCR4 promoter. These results provide the possible mechanism that E1A can function as a tumor suppressor by repressing CXCR4 mediated metastasis.