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Androgen receptor/let-7a signaling regulates breast tumor-initiating cells

2017; Impact Journals LLC; Volume: 9; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.23196

1949-2553

Wei Zhang, Xiaozhen Liu, Shan Liu, Ying Qin, Xiaoqi Tian, Fengting Niu, Han Liu, Ning Liu, Yun Niu,

Cancer-related molecular mechanisms research

// Wei Zhang 1, 2, 3, * , Xiaozhen Liu 1, * , Shan Liu 1 , Ying Qin 1 , Xiaoqi Tian 1 , Fengting Niu 1 , Han Liu 1 , Ning Liu 4 and Yun Niu 1 1 Department of Breast Cancer Pathology and Research, National Clinical Cancer Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China 2 Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China 3 Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China 4 Department of Pathology, Baodi Clinical Institute of Tianjin Medical University, Tianjin, China * These authors contributed equally to this work Correspondence to: Yun Niu, email: yunniu2000@126.com Keywords: breast cancer; androgen receptor; let-7a; tumor-initiating cells; CD44 + /24 -/low Received: October 19, 2017 Accepted: December 01, 2017 Published: December 08, 2017 ABSTRACT Androgen receptor (AR) is an important transcriptional factor, which is frequently expressed in invasive breast cancer and correlates patients’ prognosis. Our previous results indicate AR activation may increase let-7a expression in breast cancer cells, while let-7, a tumor suppressor, is reported to inhibit breast tumor-initiating cells (T-IC). The study aims to explore the effects of AR/let-7a signaling on breast T-IC and its regulatory mechanism. The results revealed that the expression of AR was significantly associated with let-7a and CD44 + /24 -/low especially in estrogen receptor positive (ER+) breast cancer tissues. The expression of AR and let-7a indicated better outcome, while patients with CD44 + /24 -/low phenotype had worse prognosis. AR activation induced by dihydrotestosterone (DHT) prevented cells proliferation, migration, invasion and self-renewal capacities in ER+ breast cancer cells, via transcriptional up-regulation of let-7a. In addition, AR could inhibit tumorigenesis and metastasis of ER+ breast cancer cells in the serial xenotranplanted animal models. Our data suggested that AR/let-7a signaling could inhibit the biological behavior of tumor-initiating cells (T-IC) in ER+AR+ breast cancers, which might become a new therapeutic target.