TNFα Induce Breast Cancer Stem Cells Through Up-regulating TAZ

Breast cancer is the most prevalent type of cancer among women worldwide.Chinese women also faced with this predicament.Breast cancer is the most common causes of cancer death among Chinese women over the age of 45.Despite advancements in the early detection and treatment of breast cancer,treated patients often suffer from disease relapse and metastasis due to the presence of breast cancer stem cells(BCSCs).In breast cancer,tumor cells can be physically separated in at least two distinct populations,one of which is enriched with BCSCs,and many studies have reported that the malignant progression of the breast cancer is often accompanied with an increased proportion of these BCSCs and Epithelial-mesenchymal transition(EMT).So,it is important to illustrate the mechanism of the producing of BCSCs.There are high levels of Inflammation factors in breast cancer.Inflammation factors,tumor necrosis factor alpha(TNFa)plays major role in breast cancer pathogenesis,progression and relapse.Furthermore,pervious studies showed that inflammation have close relationship with BCSCs.TAZ,a transcriptional co-activator tightly regulated in the hippo pathway,is required to maintain self-renewal capacity in BCSCs.In this study,we found that TNFa up-regulates TAZ and BCSCs in human breast cancer.Depletion of TAZ abrogated the increase of BCSCs.We further demonstrated that TAZ was induced by TNFa through non-canonical NFκB pathway.Our findings suggest that TAZ plays a crucial role in inflammation factors-induced BCSC increase and could serve as a promising therapeutic target.