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Upregulation of the Glutaminase II Pathway Contributes to Glutamate Production upon Glutaminase 1 Inhibition in Pancreatic Cancer.
Udupa, Sunag; Nguyen, Stephanie; Hoang, Giang; Nguyen, Tu; Quinones, Addison; Pham, Khoa; Asaka, Ryoichi; Nguyen, Kiet; Zhang, Cissy; Elgogary, Amira; Jung, Jin G; Xu, Qingguo; Fu, Jie; Thomas, Ajit G; Tsukamoto, Takashi; Hanes, Justin; Slusher, Barbara S; Cooper, Arthur J L; Le, Anne.
Afiliación
  • Udupa S; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Nguyen S; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21218, USA.
  • Hoang G; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Nguyen T; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Quinones A; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Pham K; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Asaka R; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Nguyen K; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Zhang C; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Elgogary A; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Jung JG; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Xu Q; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Fu J; Department of Ophthalmology and Wilmer Eye Institute Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Thomas AG; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Tsukamoto T; Department of Ophthalmology and Wilmer Eye Institute Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Hanes J; Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Slusher BS; Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Cooper AJL; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Le A; Department of Ophthalmology and Wilmer Eye Institute Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Proteomics ; 19(21-22): e1800451, 2019 11.
Article en En | MEDLINE | ID: mdl-31231915
The targeting of glutamine metabolism specifically via pharmacological inhibition of glutaminase 1 (GLS1) has been translated into clinical trials as a novel therapy for several cancers. The results, though encouraging, show room for improvement in terms of tumor reduction. In this study, the glutaminase II pathway is found to be upregulated for glutamate production upon GLS1 inhibition in pancreatic tumors. Moreover, genetic suppression of glutamine transaminase K (GTK), a key enzyme of the glutaminase II pathway, leads to the complete inhibition of pancreatic tumorigenesis in vivo unveiling GTK as a new metabolic target for cancer therapy. These results suggest that current trials using GLS1 inhibition as a therapeutic approach targeting glutamine metabolism in cancer should take into account the upregulation of other metabolic pathways that can lead to glutamate production; one such pathway is the glutaminase II pathway via GTK.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Inhibidores Enzimáticos / Glutaminasa / Transaminasas / Liasas Límite: Humans Idioma: En Revista: Proteomics Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Inhibidores Enzimáticos / Glutaminasa / Transaminasas / Liasas Límite: Humans Idioma: En Revista: Proteomics Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania