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Cancer Res. 2014 Feb 15;74(4):1227-37. doi: 10.1158/0008-5472.CAN-13-0594. Epub 2013 Oct 31.

Loss of androgen receptor expression promotes a stem-like cell phenotype in prostate cancer through STAT3 signaling.

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Authors' Affiliations: Departments of Molecular Medicine, Cancer Immunotherapy and Tumor Immunology, and Medical Oncology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California; and Institute for Biochemistry and Molecular Biology, Universitätsklinikum RWTH Aachen, Aachen, Germany.


Androgen receptor (AR) signaling is important for prostate cancer progression. However, androgen-deprivation and/or AR targeting-based therapies often lead to resistance. Here, we demonstrate that loss of AR expression results in STAT3 activation in prostate cancer cells. AR downregulation further leads to development of prostate cancer stem-like cells (CSC), which requires STAT3. In human prostate tumor tissues, elevated cancer stem-like cell markers coincide with those cells exhibiting high STAT3 activity and low AR expression. AR downregulation-induced STAT3 activation is mediated through increased interleukin (IL)-6 expression. Treating mice with soluble IL-6 receptor fusion protein or silencing STAT3 in tumor cells significantly reduced prostate tumor growth and CSCs. Together, these findings indicate an opposing role of AR and STAT3 in prostate CSC development.

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