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A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer.
Vidal, Samuel J; Rodriguez-Bravo, Veronica; Quinn, S Aidan; Rodriguez-Barrueco, Ruth; Lujambio, Amaia; Williams, Estrelania; Sun, Xiaochen; de la Iglesia-Vicente, Janis; Lee, Albert; Readhead, Ben; Chen, Xintong; Galsky, Matthew; Esteve, Berta; Petrylak, Daniel P; Dudley, Joel T; Rabadan, Raul; Silva, Jose M; Hoshida, Yujin; Lowe, Scott W; Cordon-Cardo, Carlos; Domingo-Domenech, Josep.
Afiliação
  • Vidal SJ; College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Rodriguez-Bravo V; Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Quinn SA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA 10032, USA.
  • Rodriguez-Barrueco R; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lujambio A; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Williams E; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Sun X; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • de la Iglesia-Vicente J; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lee A; Department of Biomedical Informatics, Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10031, USA.
  • Readhead B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Chen X; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Galsky M; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Esteve B; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Petrylak DP; Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Dudley JT; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Rabadan R; Department of Biomedical Informatics, Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10031, USA.
  • Silva JM; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hoshida Y; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lowe SW; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Cordon-Cardo C; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: carlos.cordon-cardo@mssm.edu.
  • Domingo-Domenech J; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: josep.domingo-domenech@mssm.edu.
Cancer Cell ; 27(2): 223-39, 2015 Feb 09.
Article em En | MEDLINE | ID: mdl-25670080
Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregulation of the growth hormone IGF2 emerged as a mediator of the aggressive properties regulated by GATA2. IGF2 in turn activated IGF1R and INSR as well as a downstream polykinase program. The characterization of this axis prompted a combination strategy whereby dual IGF1R/INSR inhibition restored the efficacy of chemotherapy and improved survival in preclinical models. These studies reveal a GATA2-IGF2 aggressiveness axis in lethal prostate cancer and identify a therapeutic opportunity in this challenging disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Transcrição GATA2 / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Transcrição GATA2 / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos