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Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair.
Ma, Jianhui; Benitez, Jorge A; Li, Jie; Miki, Shunichiro; Ponte de Albuquerque, Claudio; Galatro, Thais; Orellana, Laura; Zanca, Ciro; Reed, Rachel; Boyer, Antonia; Koga, Tomoyuki; Varki, Nissi M; Fenton, Tim R; Nagahashi Marie, Suely Kazue; Lindahl, Erik; Gahman, Timothy C; Shiau, Andrew K; Zhou, Huilin; DeGroot, John; Sulman, Erik P; Cavenee, Webster K; Kolodner, Richard D; Chen, Clark C; Furnari, Frank B.
Afiliação
  • Ma J; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Benitez JA; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Li J; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Miki S; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Ponte de Albuquerque C; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Galatro T; Department of Neurology, Laboratory of Molecular and Cellular Biology, LIM15, School of Medicine, University of São Paulo, São Paulo, Brazil.
  • Orellana L; Science for Life Laboratory, 17121 Stockholm, Sweden; Theoretical and Computational Biophysics, Department of Theoretical Physics, KTH Royal Institute of Technology, 106 91 Stockholm, Sweden; Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 114 18 Sto
  • Zanca C; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Reed R; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Boyer A; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Koga T; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Varki NM; Department of Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
  • Fenton TR; School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
  • Nagahashi Marie SK; Department of Neurology, Laboratory of Molecular and Cellular Biology, LIM15, School of Medicine, University of São Paulo, São Paulo, Brazil; Center for Studies of Cellular and Molecular Therapy (NAP-NETCEM-NUCEL), University of São Paulo, São Paulo, Brazil.
  • Lindahl E; Science for Life Laboratory, 17121 Stockholm, Sweden; Theoretical and Computational Biophysics, Department of Theoretical Physics, KTH Royal Institute of Technology, 106 91 Stockholm, Sweden; Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 114 18 Sto
  • Gahman TC; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Shiau AK; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • Zhou H; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
  • DeGroot J; Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Sulman EP; Departments of Radiation Oncology, Translational Molecular Pathology, and Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Cavenee WK; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA; School of Medicine, University of California at San Diego, La Jolla, CA 920
  • Kolodner RD; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA; Department of Cellular and Molecular Medicine, School of Medicine, Universi
  • Chen CC; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Furnari FB; Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pathology, School of Medicine, University of California at Sa
Cancer Cell ; 35(3): 504-518.e7, 2019 03 18.
Article em En | MEDLINE | ID: mdl-30827889
ABSTRACT
Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Prevencao_e_fatores_de_risco / Agentes_cancerigenos / Radiacao_solar / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Pirimidinas / Tolerância a Radiação / Neoplasias Encefálicas / Núcleo Celular / PTEN Fosfo-Hidrolase / Receptor Tipo 2 de Fator de Crescimento de Fibroblastos / Glioma Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Prevencao_e_fatores_de_risco / Agentes_cancerigenos / Radiacao_solar / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Pirimidinas / Tolerância a Radiação / Neoplasias Encefálicas / Núcleo Celular / PTEN Fosfo-Hidrolase / Receptor Tipo 2 de Fator de Crescimento de Fibroblastos / Glioma Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos