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Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer.
Morral, Clara; Stanisavljevic, Jelena; Hernando-Momblona, Xavier; Mereu, Elisabetta; Álvarez-Varela, Adrián; Cortina, Carme; Stork, Diana; Slebe, Felipe; Turon, Gemma; Whissell, Gavin; Sevillano, Marta; Merlos-Suárez, Anna; Casanova-Martí, Àngela; Moutinho, Catia; Lowe, Scott W; Dow, Lukas E; Villanueva, Alberto; Sancho, Elena; Heyn, Holger; Batlle, Eduard.
Afiliación
  • Morral C; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Stanisavljevic J; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Hernando-Momblona X; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08028 Barcelona, Spain.
  • Mereu E; CNAG-Centre for Genomic Regulation (CRG), BIST, Baldiri i Reixac 4, 08028 Barcelona, Spain.
  • Álvarez-Varela A; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08028 Barcelona, Spain.
  • Cortina C; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08028 Barcelona, Spain.
  • Stork D; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Slebe F; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Turon G; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Whissell G; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Sevillano M; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08028 Barcelona, Spain.
  • Merlos-Suárez A; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Casanova-Martí À; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain.
  • Moutinho C; CNAG-Centre for Genomic Regulation (CRG), BIST, Baldiri i Reixac 4, 08028 Barcelona, Spain.
  • Lowe SW; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Dow LE; Department of Medicine, Weill-Cornell Medical College, New York, NY 10021, USA.
  • Villanueva A; Group of Chemoresistance and Predictive Factors, Subprogram Against Cancer Therapeutic Resistance (ProCURE), ICO, Oncobell Program, IDIBELL, L'Hospitalet del Llobregat, 08908 Barcelona, Spain.
  • Sancho E; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08028 Barcelona, Spain.
  • Heyn H; CNAG-Centre for Genomic Regulation (CRG), BIST, Baldiri i Reixac 4, 08028 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Batlle E; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain; ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08028 Barcelona, Spain. E
Cell Stem Cell ; 26(6): 845-861.e12, 2020 06 04.
Article en En | MEDLINE | ID: mdl-32396863
Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occurs in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA polymerase I subunit A (POLR1A). Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest on CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5- tumor cells. Therefore, a common architecture in CRCs is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias Colorrectales Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2020 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias Colorrectales Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2020 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos