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Sox2 Suppresses Gastric Tumorigenesis in Mice.
Sarkar, Abby; Huebner, Aaron J; Sulahian, Rita; Anselmo, Anthony; Xu, Xinsen; Flattery, Kyle; Desai, Niyati; Sebastian, Carlos; Yram, Mary Anna; Arnold, Katrin; Rivera, Miguel; Mostoslavsky, Raul; Bronson, Roderick; Bass, Adam J; Sadreyev, Ruslan; Shivdasani, Ramesh A; Hochedlinger, Konrad.
Afiliação
  • Sarkar A; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute and Department of
  • Huebner AJ; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute and Department of
  • Sulahian R; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Anselmo A; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Xu X; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Flattery K; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute and Department of
  • Desai N; Division of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Sebastian C; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Yram MA; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute and Department of
  • Arnold K; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute and Department of
  • Rivera M; Division of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Mostoslavsky R; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Bronson R; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
  • Bass AJ; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Sadreyev R; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Shivdasani RA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Hochedlinger K; Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Howard Hughes Medical Institute and Department of
Cell Rep ; 16(7): 1929-41, 2016 08 16.
Article em En | MEDLINE | ID: mdl-27498859
Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. By using ChIP-seq analysis, we have found that the majority of Sox2 targets in gastric epithelial cells are tissue specific and related to functions such as endoderm development, Wnt signaling, and gastric cancer. Unexpectedly, we found that Sox2 itself is dispensable for gastric stem cell and epithelial self-renewal, yet Sox2(+) cells are highly susceptible to tumorigenesis in an Apc/Wnt-driven mouse model. Moreover, Sox2 loss enhances, rather than impairs, tumor formation in Apc-deficient gastric cells in vivo and in vitro by inducing Tcf/Lef-dependent transcription and upregulating intestinal metaplasia-associated genes, providing a mechanistic basis for the observed phenotype. Together, these data identify Sox2 as a context-dependent tumor suppressor protein that is dispensable for normal tissue regeneration but restrains stomach adenoma formation through modulation of Wnt-responsive and intestinal genes.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Adenoma / Regulação Neoplásica da Expressão Gênica / Transformação Celular Neoplásica / Proteína da Polipose Adenomatosa do Colo / Fatores de Transcrição SOXB1 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Adenoma / Regulação Neoplásica da Expressão Gênica / Transformação Celular Neoplásica / Proteína da Polipose Adenomatosa do Colo / Fatores de Transcrição SOXB1 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2016 Tipo de documento: Article