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Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence.
Wu, Zhong; Zhou, Jin; Zhang, Xiaoyang; Zhang, Zhouwei; Xie, Yingtian; Liu, Jie Bin; Ho, Zandra V; Panda, Arpit; Qiu, Xintao; Cejas, Paloma; Cañadas, Israel; Akarca, Fahire Goknur; McFarland, James M; Nagaraja, Ankur K; Goss, Louisa B; Kesten, Nikolas; Si, Longlong; Lim, Klothilda; Liu, Yanli; Zhang, Yanxi; Baek, Ji Yeon; Liu, Yang; Patil, Deepa T; Katz, Jonathan P; Hai, Josephine; Bao, Chunyang; Stachler, Matthew; Qi, Jun; Ishizuka, Jeffrey J; Nakagawa, Hiroshi; Rustgi, Anil K; Wong, Kwok-Kin; Meyerson, Matthew; Barbie, David A; Brown, Myles; Long, Henry; Bass, Adam J.
Afiliação
  • Wu Z; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zhou J; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Zhang X; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zhang Z; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Xie Y; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Liu JB; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Ho ZV; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Panda A; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Qiu X; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Cejas P; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Cañadas I; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Akarca FG; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • McFarland JM; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Nagaraja AK; Committee on Immunology, The University of Chicago, Chicago, IL, USA.
  • Goss LB; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Kesten N; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Si L; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Lim K; Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
  • Liu Y; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zhang Y; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Baek JY; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Liu Y; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Patil DT; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Katz JP; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Hai J; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Bao C; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Stachler M; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
  • Qi J; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Ishizuka JJ; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Nakagawa H; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Rustgi AK; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Wong KK; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Meyerson M; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Barbie DA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Brown M; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Long H; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Bass AJ; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nat Genet ; 53(6): 881-894, 2021 06.
Article em En | MEDLINE | ID: mdl-33972779
Esophageal squamous cell carcinomas (ESCCs) harbor recurrent chromosome 3q amplifications that target the transcription factor SOX2. Beyond its role as an oncogene in ESCC, SOX2 acts in development of the squamous esophagus and maintenance of adult esophageal precursor cells. To compare Sox2 activity in normal and malignant tissue, we developed engineered murine esophageal organoids spanning normal esophagus to Sox2-induced squamous cell carcinoma and mapped Sox2 binding and the epigenetic and transcriptional landscape with evolution from normal to cancer. While oncogenic Sox2 largely maintains actions observed in normal tissue, Sox2 overexpression with p53 and p16 inactivation promotes chromatin remodeling and evolution of the Sox2 cistrome. With Klf5, oncogenic Sox2 acquires new binding sites and enhances activity of oncogenes such as Stat3. Moreover, oncogenic Sox2 activates endogenous retroviruses, inducing expression of double-stranded RNA and dependence on the RNA editing enzyme ADAR1. These data reveal SOX2 functions in ESCC, defining targetable vulnerabilities.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Adenosina Desaminase / Proteínas de Ligação a RNA / Fatores de Transcrição SOXB1 / Carcinoma de Células Escamosas do Esôfago / Epigenoma Limite: Animals / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Adenosina Desaminase / Proteínas de Ligação a RNA / Fatores de Transcrição SOXB1 / Carcinoma de Células Escamosas do Esôfago / Epigenoma Limite: Animals / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos