TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.
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Groner AC
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
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Cato L
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
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de Tribolet-Hardy J
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
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Bernasocchi T
Institute of Oncology Research, Bellinzona 6500, Switzerland.
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Janouskova H
Institute of Oncology Research, Bellinzona 6500, Switzerland.
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Melchers D
PamGene International, Den Bosch 521HH, the Netherlands.
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Houtman R
PamGene International, Den Bosch 521HH, the Netherlands.
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Cato ACB
Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany.
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Tschopp P
Department of Genetics, Harvard Medical School, Boston, MA 02215, USA.
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Gu L
Division of Newborn Medicine, Children's Hospital Boston and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
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Corsinotti A
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH16 4UU, UK; Laboratory Animal Resource Center, Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
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Zhong Q
Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
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Fankhauser C
Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland; Department of Urology, University Hospital Zurich, Zurich 8091, Switzerland.
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Fritz C
Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
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Poyet C
Department of Urology, University Hospital Zurich, Zurich 8091, Switzerland.
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Wagner U
Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
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Guo T
Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich 8093, Switzerland.
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Aebersold R
Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich 8093, Switzerland; Faculty of Science, University of Zurich, Zurich 8057, Switzerland.
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Garraway LA
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
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Wild PJ
Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
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Theurillat JP
Institute of Oncology Research, Bellinzona 6500, Switzerland; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne 1011, Switzerland. Electronic address: jeanp_theurillat@ior.iosi.ch.
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Brown M
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: myles_brown@dfci.harvard.edu.
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English
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in speckle-type POZ protein (SPOP) stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly upregulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP mutant and CRPC patients.
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Language
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Open access status
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bronze
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Persistent URL
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https://folia.unifr.ch/global/documents/168112
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