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Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer.
Stoyanova, Tanya; Riedinger, Mireille; Lin, Shu; Faltermeier, Claire M; Smith, Bryan A; Zhang, Kelvin X; Going, Catherine C; Goldstein, Andrew S; Lee, John K; Drake, Justin M; Rice, Meghan A; Hsu, En-Chi; Nowroozizadeh, Behdokht; Castor, Brandon; Orellana, Sandra Y; Blum, Steven M; Cheng, Donghui; Pienta, Kenneth J; Reiter, Robert E; Pitteri, Sharon J; Huang, Jiaoti; Witte, Owen N.
Afiliação
  • Stoyanova T; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; stanya@stanford.edu owenwitte@mednet.ucla.edu.
  • Riedinger M; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095.
  • Lin S; Department of Urology, University of California, Los Angeles, CA 90095.
  • Faltermeier CM; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
  • Smith BA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
  • Zhang KX; Department of Biological Chemistry, University of California, Los Angeles, CA 90095.
  • Going CC; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304.
  • Goldstein AS; Department of Urology, University of California, Los Angeles, CA 90095; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 900
  • Lee JK; Division of Hematology and Medical Oncology, University of California, Los Angeles, CA 90095.
  • Drake JM; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903; Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, 08901.
  • Rice MA; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304.
  • Hsu EC; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304.
  • Nowroozizadeh B; Department of Pathology, University of California, Irvine, CA 92697; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.
  • Castor B; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.
  • Orellana SY; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
  • Blum SM; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA 02115.
  • Cheng D; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095.
  • Pienta KJ; Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287.
  • Reiter RE; Department of Urology, University of California, Los Angeles, CA 90095.
  • Pitteri SJ; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94304.
  • Huang J; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pathology, Duke University School of Medicine, Durham, NC 27710.
  • Witte ON; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University
Proc Natl Acad Sci U S A ; 113(42): E6457-E6466, 2016 10 18.
Article em En | MEDLINE | ID: mdl-27694579
ABSTRACT
Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Receptor Notch1 / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Receptor Notch1 / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2016 Tipo de documento: Article