title: Notch3 negatively regulates chemoresistance in breast cancers.
abstract: To define the role of the NOTCH signaling pathway in the development of chemoresistance and the associated epithelial-mesenchymal transition (EMT), we investigated the effect of Notch3 on adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM cells). We found that Notch3 was downregulated and involved in the chemoresistance of MCF-7/ADM cells, while forced expression of Notch3 reversed the chemoresistance. Furthermore, fos-related antigen 1 (Fra1) was negatively regulated by Notch3 and was highly expressed in MCF-7/ADM cells. Increased Fra1 activated the EMT process. Finally, Notch3 expression was confirmed in clinically chemoresistant samples of breast cancers from patients receiving anthracycline-based chemotherapy. Low expression of Notch3 was an unfavorable predictor of distant relapse-free survival in ER positive breast cancers. Taken together, our findings demonstrate that the Notch3-Fra1 signaling pathway mediates chemoresistance via the EMT.
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu, 214122, China.
authors.forename: Xiaoting
authors.identifier: 0000-0001-5832-2078
authors.initials: X
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu, 214122, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Lu
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, 214122, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: He
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu, 214122, China.
authors.forename: Yangfan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu, 214122, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University, Kunming, China. dequanliu08@163.com.
authors.forename: Dequan
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu, 214122, China. maxin@jiangnan.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
keywords: Breast cancer; Chemoresistance; EMT; Fra1; Notch3