Tamoxifen enhances stemness and promotes metastasis of ERa36 breast cancer by upregulating ALDHIA1 in cancer cells  

作　　者：Qiang Wang1＇ 2, Jun Jiang3, Guoguang Ying4, Xiao-Qing Xiel＇ 2, Xia Zhang1＇ 2 Wei Xul＇ 2, 5 Xuemin Zhang6, Erwei Song7, Hong Bun, Yi-Fang Ping1＇ 2, Xiao-Hong Yao1＇ 2, Bin Wang1＇ 2, Shilei Xu4, Ze-Xuan Yan1＇ 2, Yanhong Tai9, Baoquan Hu3, Xiaowei Qi3, Yan-Xia Wangl＇ 2, Zhi-Cheng He1＇ 2, Yan Wang1＇ 2, Ji Ming Wang, You-Hong Cui1＇ 2, Feng ChenI2, Kun Meng12, Zhaoyi Wang1＇ 2, 13, Xiu-Wu Bian1＇ 2 

机构地区：Institute of Pathology and Southwest Cancer Center, Southwest Hospital Third Military Medical University （Army Medical Uni- versity）, Chongqing 400038, China 2Key Laboratory of Tumor lmmunopathology, Ministry of Education of China, Chongqing 400038, China 3Department of Breast Diseases, Southwest Cancer Center, Southwest Hospital Third Military Medical University, Chongqing 400038, China 4Laboratory of Cancer Cell Biology, Tianjin Cancer Institute, Tianjin Medical University Cancer Insti- tute and Hospital Tianjin 300060, China SMcArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, W1 53706, USA 6State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, China National Center of Biomedi- cal Analysis, Beijing 100850, China 7Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120,＇China,＂ 8Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China, 9Department of Pathology, General Hospital of PLA, Beo＇ing 100853, China 1Department of Pathology, No.307 Hospital of PLA, Beoing 100071, China 11Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA 12Shenogen Pharma Group, Beijing 100085, China l SDepartments of Medical Mi- crobiology ＆ Immunology, Creighton University Medical School, 2500 California Plaza, Omaha, NE 68178, USA

出　　处：《Cell Research》2018年第3期336-358,共23页细胞研究（英文版）

摘　　要：The 66 kDa estrogen receptor alpha （ERa66） is the main molecular target for endocrine therapy such as tamoxi- fen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERa36, a variant of ERa66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERa36 to enhance the sternness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 （ALD- H1A1）. Consistently, the tamoxifen-induced sternness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERa36 antibody. Thus, tamoxifen acts as an agonist on ERa36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERa36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer.

关 键 词：breast cancer estrogen receptor cancer stem cells METASTASIS endocrine therapy 

分 类 号：S854.5[农业科学—临床兽医学] TQ467[农业科学—兽医学]