机构：[1]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.[2]Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.[3]Department of Breast Diseases, Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.[4]Laboratory of Cancer Cell Biology, Tianjin Cancer Institute, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.[5]McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.[6]State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, China National Center of Biomedical Analysis, Beijing 100850, China.[7]Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.中山大学附属第二医院[8]Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[9]Department of Pathology, General Hospital of PLA, Beijing 100853, China.[10]Department of Pathology, No.307 Hospital of PLA, Beijing 100071, China.[11]Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.[12]Shenogen Pharma Group, Beijing 100085, China.[13]Departments of Medical Microbiology &[14]Immunology, Creighton University Medical School, 2500 California Plaza, Omaha, NE 68178, USA.
The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen 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 ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer.
基金：
National Key Research and
Development Program (2016YFA0101200), the National Natural
Science Foundation of China (61327902-04, 81502283, 81071771,
81230062).
第一作者机构：[1]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.[2]Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.[2]Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China.
推荐引用方式(GB/T 7714)：
Wang Qiang,Jiang Jun,Ying Guoguang,et al.Tamoxifen enhances stemness and promotes metastasis of ERα36+ breast cancer by upregulating ALDH1A1 in cancer cells.[J].CELL RESEARCH.2018,28(3):336-358.doi:10.1038/cr.2018.15.
APA：
Wang Qiang,Jiang Jun,Ying Guoguang,Xie Xiao-Qing,Zhang Xia...&Bian Xiu-Wu.(2018).Tamoxifen enhances stemness and promotes metastasis of ERα36+ breast cancer by upregulating ALDH1A1 in cancer cells..CELL RESEARCH,28,(3)
MLA：
Wang Qiang,et al."Tamoxifen enhances stemness and promotes metastasis of ERα36+ breast cancer by upregulating ALDH1A1 in cancer cells.".CELL RESEARCH 28..3(2018):336-358
生物