Nrf2 Regulates Breast Cancer Proliferation And Migration Through Metabolic Reprogramming And Notch Signaling Pathway

Breast cancer is a disease affecting women's health seriously.Recent studies have shown that the abnormal metabolism of tumor cells is closely related to the occurrence and development of tumors.Nrf2 [nuclear factor erythroid 2(NFE2)related factor 2] is an important antioxidant stress factor.The expression of Nrf2 plays an important role in cancer cells occurrence and development.Nrf2 has become one of the highlights in agro-scientific research of the cell biology and tumor biology through regulating tumor metabolic to regulate of cancer cell growth.The main purpose of this study was to understand the effect of Nrf2 on the metabolic reprogramming of breast cancer cells and search for the effect and mechanism of Nrf2 on the proliferation and migration of breast cancer.In this study,we found that the expression of Nrf2 in breast cancer cells MCF-7 and MDA-MB-231 was significantly higher than that in MCF-10 A cells.Inhibition of Nrf2 could reduce the expression of glycolytic enzymes,including HK2,PFKFB3,PKM2 and LDHA,in breast caner cells.Overexpression of Nrf2 in MCF-10 A would enhance the expression level of glycolysis.Inhibition of Nrf2 could also reduce the expression of G6 PD and TKT of pentose phosphate pathway,and overexpression of Nrf2 also activated the expression level of pentose phosphate pathway in breast cancer cells.This indicates that Nrf2 can promote metabolic reprogramming in breast cancer.Our results further indicated that overexpression of Nrf2 could promote the expression of G6 PD,and then reduced the level of ROS in the cells.Thus inducing the increase of the expression level of the hypoxia inducible factor-1(hypoxia inducible factor-1,HIF-1),and then up-regulated the expression of Notch1,which affects the expression of the Notch signaling pathway.Notch signaling pathway affected the proliferation of breast cancer by affecting its downstream gene HES-1,and regulated the migration of breast cancer cells by affecting the expression of EMT pathway.In summary,we have found that Nrf2 can promote the metabolic reprogramming of breast cancer cells and play a key role in tumor proliferation and metastasis.These results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer.