The Mechanism That FoxO Regulates Breast Cancer Metastasis Through DME

Breast cancer is No.1 killer of women worldwide.There has been a significant rise in morbidity and mortality from breast cancer in China in the past years.The FoxO proteins are a class of large group of forkhead transcription factors,which are all characterized by a conserved DNA-binding domain.FoxO proteins have been validated to be tumor suppressors for their roles in cell-cycle arrest,apoptosis,DNA-damage repair.The DME protein was supposed to be a tumor suppressor for its role in maintaining genomic DNA stability through the way of epigenetic regulation.We have seen that more advanced cancers are correlated with higher level cytokines in tumor microenviroment in many researches.Chemokines,which belongs to cytokines,may promotes breast tumor growth and metastasis through inducing the recruitment of monocytes from the tumor circulation into tumor sites.However,it is still unclear that how the FoxO proteins regulate the methylation of DNA and the secretion of cytokines to infect breast cancer metastasis.Here,we find that FoxO directly induces DME gene expression in breast cancer cells through binding to the promoter regions of DME gene.FoxO or DME depletion resulted in CCLX up-regulation.We further hypothesized that FoxO may suppress the expression of CCLX through inducing the expression of DME.However,the mechanism of how DME regulates the secretion of CCLX remains unclear.What we want to show is that the FoxO/DME/CCLX signaling pathway can suppress the metastasis of breast cancer cells.