Divergent Androgen Receptor and Beta-Catenin Signaling in Prostate Cancer Cells.
Despite decades of effort to develop effective therapy and to identify promising new drugs, prostate cancer is lethal once it progresses to castration-resistant disease. Studies show mis-regulation of multiple pathways in castration-resistant prostate cancer (CRPC), reflecting the heterogeneity of the tumors and also hinting that targeting androgen receptor (AR) pathway alone might not be sufficient to treat CRPC. In this study, we present evidence that the Wnt/β-catenin pathway might be activated in prostate cancer cells after androgen-deprivation to promote androgen-independent growth, partly through enhanced interaction of β-catenin with TCF4. Androgen-independent prostate cancer cells were more prone to activate a Wnt-reporter, and inhibition of the Wnt/β-catenin pathway increased sensitivity of these cells to the second-generation antiandrogen, enzalutamide. Combined treatment of enzalutamide and Wnt/β-catenin inhibitor showed increased growth repression in both androgen-dependent and -independent prostate cancer cells, suggesting therapeutic potential for this approach.
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America; Stem Cell Biology Program, New York University School of Medicine, New York, NY, United States of America.
Eugine
E
Lee
Department of Urology New York University School of Medicine, New York, NY, United States of America.
Susan
S
Ha
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America; Department of Urology New York University School of Medicine, New York, NY, United States of America; Stem Cell Biology Program, New York University School of Medicine, New York, NY, United States of America.
Susan K
SK
Logan
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D011471:Prostatic Neoplasms; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C410798:AR protein, human; D011944:Receptors, Androgen; D051176:beta Catenin