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Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells.
Newman, Alice Clare; Falcone, Mattia; Huerta Uribe, Alejandro; Zhang, Tong; Athineos, Dimitris; Pietzke, Matthias; Vazquez, Alexei; Blyth, Karen; Maddocks, Oliver David Kenneth.
Afiliação
  • Newman AC; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK.
  • Falcone M; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK.
  • Huerta Uribe A; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK.
  • Zhang T; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK.
  • Athineos D; Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
  • Pietzke M; Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
  • Vazquez A; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK; Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
  • Blyth K; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK; Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
  • Maddocks ODK; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK. Electronic address: oliver.maddocks@glasgow.ac.uk.
Mol Cell ; 81(11): 2290-2302.e7, 2021 06 03.
Article em En | MEDLINE | ID: mdl-33831358
Cancer cells adapt their metabolism to support elevated energetic and anabolic demands of proliferation. Folate-dependent one-carbon metabolism is a critical metabolic process underpinning cellular proliferation supplying carbons for the synthesis of nucleotides incorporated into DNA and RNA. Recent research has focused on the nutrients that supply one-carbons to the folate cycle, particularly serine. Tryptophan is a theoretical source of one-carbon units through metabolism by IDO1, an enzyme intensively investigated in the context of tumor immune evasion. Using in vitro and in vivo pancreatic cancer models, we show that IDO1 expression is highly context dependent, influenced by attachment-independent growth and the canonical activator IFNγ. In IDO1-expressing cancer cells, tryptophan is a bona fide one-carbon donor for purine nucleotide synthesis in vitro and in vivo. Furthermore, we show that cancer cells release tryptophan-derived formate, which can be used by pancreatic stellate cells to support purine nucleotide synthesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Evasão Tumoral / Carcinoma Ductal Pancreático / Indolamina-Pirrol 2,3,-Dioxigenase / Células Estreladas do Pâncreas Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Evasão Tumoral / Carcinoma Ductal Pancreático / Indolamina-Pirrol 2,3,-Dioxigenase / Células Estreladas do Pâncreas Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2021 Tipo de documento: Article