ATF3 Activates Stat3 Phosphorylation through Inhibition of p53 Expression in Skin Cancer Cells

Abstract

Aim: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectivelyinduced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the preciserole of ATF3 in human skin cancer and possible mechanisms remain unknown. <br/><b>Methods</b>: In this study, clinicalanalysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancertissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. <br/><b>Results</b>:Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression.Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signalingcascade. <br/><b>Conclusion</b>: Together, the results indicate that ATF3 might promote skin cancer cell proliferation andenhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3phosphorylation.