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Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells.
Belcheva, Antoaneta; Irrazabal, Thergiory; Robertson, Susan J; Streutker, Catherine; Maughan, Heather; Rubino, Stephen; Moriyama, Eduardo H; Copeland, Julia K; Surendra, Anu; Kumar, Sachin; Green, Blerta; Geddes, Kaoru; Pezo, Rossanna C; Navarre, William W; Milosevic, Michael; Wilson, Brian C; Girardin, Stephen E; Wolever, Thomas M S; Edelmann, Winfried; Guttman, David S; Philpott, Dana J; Martin, Alberto.
Afiliação
  • Belcheva A; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Irrazabal T; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Robertson SJ; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Streutker C; Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
  • Maughan H; Ronin Institute, Montclair, NJ 07043, USA.
  • Rubino S; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Moriyama EH; Princess Margaret Cancer Centre/University Health Network, Toronto, ON M5G 1L7, Canada.
  • Copeland JK; Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, ON M5S 3B2, Canada.
  • Surendra A; Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, ON M5S 3B2, Canada.
  • Kumar S; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Green B; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Geddes K; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Pezo RC; Department of Medical Oncology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Navarre WW; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Milosevic M; Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.
  • Wilson BC; Princess Margaret Cancer Centre/University Health Network, Toronto, ON M5G 1L7, Canada.
  • Girardin SE; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Wolever TMS; Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 3E2, Canada.
  • Edelmann W; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Guttman DS; Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, ON M5S 3B2, Canada.
  • Philpott DJ; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Martin A; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: alberto.martin@utoronto.ca.
Cell ; 158(2): 288-299, 2014 Jul 17.
Article em En | MEDLINE | ID: mdl-25036629
The etiology of colorectal cancer (CRC) has been linked to deficiencies in mismatch repair and adenomatous polyposis coli (APC) proteins, diet, inflammatory processes, and gut microbiota. However, the mechanism through which the microbiota synergizes with these etiologic factors to promote CRC is not clear. We report that altering the microbiota composition reduces CRC in APC(Min/+)MSH2(-/-) mice, and that a diet reduced in carbohydrates phenocopies this effect. Gut microbes did not induce CRC in these mice through an inflammatory response or the production of DNA mutagens but rather by providing carbohydrate-derived metabolites such as butyrate that fuel hyperproliferation of MSH2(-/-) colon epithelial cells. Further, we provide evidence that the mismatch repair pathway has a role in regulating ß-catenin activity and modulating the differentiation of transit-amplifying cells in the colon. These data thereby provide an explanation for the interaction between microbiota, diet, and mismatch repair deficiency in CRC induction. PAPERCLIP:
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carboidratos da Dieta / Neoplasias Colorretais / Proteína 2 Homóloga a MutS Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carboidratos da Dieta / Neoplasias Colorretais / Proteína 2 Homóloga a MutS Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Canadá