ArticleNature genetics2021
Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence.
Open access · greenAbstract read
In one paragraph
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
8.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- A systematic review of observational studies on long-term air pollution exposure and epigenetic alterations in adults.Journal of global health · 2026Pooled it
- Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.Nature communications · 2026Article
- ADAR1 regulates radiosensitivity in ESCC through cIAP2-NF-κB signaling and C16orf46 editing.iScience · 2026Article
- Disrupting SOX2 self-association and condensate formation to overcome chemotherapeutic drug resistance in lung squamous cell carcinoma.Signal transduction and targeted therapy · 2026Article
- Viral mimicry acts as a tumor suppressor in colitis.Nature communications · 2026Article
- Deep learning-based multimodal pathogenomics integration for precision cancer prognosis.Journal of translational medicine · 2026Article
- Clonal evolution in gastrointestinal cancers: multi-omics insights into tumor heterogeneity, microenvironmental selection, and translational biomarkers.Frontiers in oncology · 2026Review
- Integrative Analysis Identified an Eight-Gene Risk Signature Linked to CDK7 and Explored Its Association with HCC Progression via RelA Phosphorylation.Oncology research · 2026Article
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- Co-activation of the super-enhancer complex SOX2 and HDAC1 confers temozolomide resistance by promoting PDGFB transcription in glioblastoma.Neuro-oncology · 2026Article
- Single-Cell Lineage Trajectory Defines Cyclin-Dependent Kinase Inhibitor-Sensitive Cells-of-Origin in Esophageal Squamous Cell Carcinoma.Gastro hep advances · 2026Article
- Enhancer Reprogramming Reveals the Tumorigenic Role of PTPRZ1 in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Genetic Engineering of Esophageal Organoids: CRISPR-Based Knock-In for Cell Lineage Tracing.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers.Nature communications · 2025Article
- Decursin Suppresses Esophageal Squamous Cell Carcinoma Progression via Orchestrated Cell Cycle Deceleration, Apoptotic Activation, and Oncoprotein Degradation.International journal of molecular sciences · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy.Cancer cell · 2025Review
- KLF5 promotes esophageal squamous cell carcinoma radioresistance by targeting the Keap1-Nrf2 pathway.Discover oncology · 2025Article
- Deciphering the generation of heterogeneity in esophageal squamous cell carcinoma metastasis via single-cell multiomics analysis.Journal of translational medicine · 2025Article
- Inhibition of KLF5 promotes ferroptosis via the ZEB1/HMOX1 axis to enhance sensitivity to oxaliplatin in cancer cells.Cell death & disease · 2025Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 7 institutions in 1 country.
Zhong Wu *Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jin Zhou *Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Xiaoyang Zhang *Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0031-0290
Zhouwei ZhangDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yingtian XieCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jie Bin LiuDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Zandra V HoCancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4046-0266
Arpit PandaDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Xintao QiuCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8560-7017
Paloma CejasCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Israel CañadasDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Fahire Goknur AkarcaDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2254-3279
James M McFarlandCancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9978-480X
Ankur K NagarajaDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8586-3117
Louisa B GossDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nikolas KestenDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Longlong SiWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Klothilda LimCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yanli LiuDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Yanxi ZhangDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Ji Yeon BaekDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yang LiuDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Deepa T PatilDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Jonathan P KatzDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6922-1707
Josephine HaiDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Chunyang BaoDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7962-346X
Matthew StachlerDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jun QiCancer Biology Department, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1461-3356
Jeffrey J IshizukaDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Hiroshi NakagawaHerbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, USA.
Anil K RustgiHerbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, USA.
Kwok-Kin WongDivision of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-6323-235X
Matthew MeyersonDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
David A BarbieDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Myles BrownDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Henry LongCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6849-6629
Adam J BassDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. ab5147@cumc.columbia.edu.ORCID http://orcid.org/0000-0002-8193-4758
Harvard University · USBroad Institute · USBrigham and Women's Hospital · USColumbia University Irving Medical Center · USFox Chase Cancer Center · USNYU Langone Health · USUniversity of Pennsylvania · US
Funding
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI REBECCA G WELLS · 1997 to 2026
$32.5MTransformed Esophageal Epithelial Cells and the Tumor MicroenvironmentP01CA098101 · NCI · UNIVERSITY OF PENNSYLVANIA · PI HIBSHOOSH, HANINA · 2003 to 2023
$31.7MTherapeutic targeting of Fibroblast Growth Factor Receptors in Squamous CancersR01CA196932 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2015 to 2019
$1.9MNovel Roles for Oncogenic SOX2 in Esophageal Squamous Cell CarcinomaR01CA187119 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2015 to 2019
$1.9MKLF4 and WNT5A in esophageal epithelial differentiation and stratificationR01DK119314 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATZ, JONATHAN P · 2019 to 2022
$1.5MTriggering Innate Immunity in Tumor Cells to Overcome Resistance to ImmunotherapyK08CA245112 · NCI · YALE UNIVERSITY · PI ISHIZUKA, JEFFREY J. · 2020 to 2024
$1.3MInvestigating the role of KLF5 genomic alterations in tumorigenesisR00CA215244 · NCI · UNIVERSITY OF UTAH · PI ZHANG, XIAOYANG · 2019 to 2021
$742kNCI NIH HHS K08 CA245112NCI NIH HHS P01 CA098101NCI NIH HHS R00 CA215244NCI NIH HHS R01 CA187119NCI NIH HHS R01 CA196932NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK119314
Abstract
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.
Indexed as
Epigenome3' Untranslated RegionsAdenosine DeaminaseAnimalsBase SequenceCarcinogenesisCell Line, TumorCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p16Endogenous RetrovirusesEnhancer Elements, GeneticEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaGene Expression Regulation, NeoplasticGenome, HumanHumans3' Untranslated RegionsADAR protein, humanAdenosine DeaminaseCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16InterferonsKLF5 protein, humanKruppel-Like Transcription FactorsRNA-Binding ProteinsRNA, Double-StrandedSOX2 protein, humanSOXB1 Transcription FactorsTumor Suppressor Protein p53
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.