title: YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer.
abstract: The transcriptional co-activator Yes-associated protein 1 (YAP1), a key nuclear effector of the Hippo pathway, is a potent oncogene, and yet, the interaction between YAP1 and androgen receptor (AR) remains unexplored. Here we identify YAP1 as a physiological binding partner and positive regulator of AR in prostate cancer. YAP1 and AR co-localize and interact with each other predominantly within cell nuclei by an androgen-dependent mechanism in a hormone naive and an androgen-independent mechanism in castration-resistant prostate cancer cells. The growth suppressor MST1 kinase modulates androgen-dependent and -independent nuclear YAP1-AR interactions through directly regulating YAP1 nuclear accumulation. Disruption of YAP1 signalling by genetic (RNAi) and pharmacological (Verteporfin) approaches suppresses AR-dependent gene expression and prostate cancer cell growth. These findings indicate that the YAP1-AR axis may have a critical role in prostate cancer progression and serves as a viable drug target.
authors.affiliation: Department of Medicine-Hematology and Oncology and Biomedical Sciences, Cancer Biology and Uro-Oncology Programs, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Gamze
authors.initials: G
authors.lastname: Kuser-Abali
authors.affiliation: Department of Medicine-Hematology and Oncology and Biomedical Sciences, Cancer Biology and Uro-Oncology Programs, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Alptekin
authors.affiliation: West Los Angeles Veteran Affairs Healthcare System, Los Angeles, California 90073, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lewis
authors.affiliation: West Los Angeles Veteran Affairs Healthcare System, Los Angeles, California 90073, USA.|Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, California 90095, USA.
authors.forename: Isla P
authors.initials: IP
authors.lastname: Garraway
authors.affiliation: Department of Medicine-Hematology and Oncology and Biomedical Sciences, Cancer Biology and Uro-Oncology Programs, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.|West Los Angeles Veteran Affairs Healthcare System, Los Angeles, California 90073, USA.|Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.|Department of Biological Sciences and Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, Georgia 30314, USA.
authors.forename: Bekir
authors.initials: B
authors.lastname: Cinar