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Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier.
Bensard, Claire L; Wisidagama, Dona R; Olson, Kristofor A; Berg, Jordan A; Krah, Nathan M; Schell, John C; Nowinski, Sara M; Fogarty, Sarah; Bott, Alex J; Wei, Peng; Dove, Katja K; Tanner, Jason M; Panic, Vanja; Cluntun, Ahmad; Lettlova, Sandra; Earl, Christian S; Namnath, David F; Vázquez-Arreguín, Karina; Villanueva, Claudio J; Tantin, Dean; Murtaugh, L Charles; Evason, Kimberley J; Ducker, Gregory S; Thummel, Carl S; Rutter, Jared.
Afiliação
  • Bensard CL; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Wisidagama DR; Department of Human Genetics, University of Utah, Salt Lake City, UT 84132, USA.
  • Olson KA; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Berg JA; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Krah NM; Department of Human Genetics, University of Utah, Salt Lake City, UT 84132, USA.
  • Schell JC; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Nowinski SM; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Fogarty S; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Bott AJ; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Wei P; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Dove KK; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Tanner JM; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Panic V; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Cluntun A; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Lettlova S; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Earl CS; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Namnath DF; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Vázquez-Arreguín K; Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA.
  • Villanueva CJ; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Tantin D; Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA.
  • Murtaugh LC; Department of Human Genetics, University of Utah, Salt Lake City, UT 84132, USA.
  • Evason KJ; Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA.
  • Ducker GS; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
  • Thummel CS; Department of Human Genetics, University of Utah, Salt Lake City, UT 84132, USA. Electronic address: carl.thummel@genetics.utah.edu.
  • Rutter J; Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA; Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. Electronic address: rutter@biochem.utah.edu.
Cell Metab ; 31(2): 284-300.e7, 2020 02 04.
Article em En | MEDLINE | ID: mdl-31813825
ABSTRACT
Although metabolic adaptations have been demonstrated to be essential for tumor cell proliferation, the metabolic underpinnings of tumor initiation are poorly understood. We found that the earliest stages of colorectal cancer (CRC) initiation are marked by a glycolytic metabolic signature, including downregulation of the mitochondrial pyruvate carrier (MPC), which couples glycolysis and glucose oxidation through mitochondrial pyruvate import. Genetic studies in Drosophila suggest that this downregulation is required because hyperplasia caused by loss of the Apc or Notch tumor suppressors in intestinal stem cells can be completely blocked by MPC overexpression. Moreover, in two distinct CRC mouse models, loss of Mpc1 prior to a tumorigenic stimulus doubled the frequency of adenoma formation and produced higher grade tumors. MPC loss was associated with a glycolytic metabolic phenotype and increased expression of stem cell markers. These data suggest that changes in cellular pyruvate metabolism are necessary and sufficient to promote cancer initiation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenoma / Ácido Pirúvico / Proteínas de Transporte da Membrana Mitocondrial / Carcinogênese / Mitocôndrias Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenoma / Ácido Pirúvico / Proteínas de Transporte da Membrana Mitocondrial / Carcinogênese / Mitocôndrias Idioma: En Ano de publicação: 2020 Tipo de documento: Article