Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors
Open accessAbstract
KDM6A, an X chromosome-encoded histone demethylase and member of the COMPASS-like complex, is frequently mutated in a broad spectrum of malignancies and contributes to oncogenesis with poorly characterized mechanisms. We found that KDM6A loss induced squamous-like, metastatic pancreatic cancer selectively in females through deregulation of the COMPASS-like complex and aberrant activation of super-enhancers regulating ΔNp63, MYC, and RUNX3 oncogenes. This subtype of tumor developed in males had concomitant loss of UTY and KDM6A, suggesting overlapping roles, and points to largely demethylase independent tumor suppressor functions. We also demonstrate that KDM6A-deficient pancreatic cancer is selectively sensitive to BET inhibitors, which reversed squamous differentiation and restrained tumor growth in vivo, highlighting a therapeutic niche for patient tailored therapies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Deletion of KDM6A in GEMMs results in accelerated tumorigenesis and acquisition of an aggressive transcriptional subtype.
“deletion of KDM6A results in accelerated tumorigenesis and acquisition of an aggressive transcriptional subtype95–97.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [97]
TP63 can promote more aggressive PDAC subtypes and can be induced by KDM6A loss.
“several candidate regulators such as TP63136, which can be induced by KDM6A loss97, can promote more aggressive subtypes”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [97]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 79 · Cited by 320
- Authors
- Andricovich, J., Perkail, S., Kai, Y., Casasanta, N., Peng, W., & Tzatsos, A.
- Affiliations
- George Washington University (US)
- Corresponding author
- Tzatsos, Alexandros
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 33
- Issue
- 3
- Pages
- 512-526.e8
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC5854186
- OpenAlex
- W2791796258
- Cited by
- 320
- References
- 79
- Citations by year
- 2026: 28 · 2025: 42 · 2024: 32 · 2023: 43 · 2022: 40 · 2021: 53 · 2020: 39 · 2019: 26 · 2018: 16
- FWCI
- 11.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Institute for Biomedical Sciences
- Columbian College of Arts and Sciences
- GWU Cross-Disciplinary Research Fund
- NIAID (R21AI113806, R01AI121080)
- Hirshberg Foundation for Pancreatic Cancer Research
- GWU Cancer Center
- National Cancer Institute (R00CA158582, R21CA182662, R03CA212068)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- KDM6A, pancreatic cancer, super-enhancers, histone demethylase, ΔNp63, c-Myc, RUNX3, UTY, BET inhibitors, tumor suppressor function, squamous differentiation, metastatic pancreatic cancer
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Humans, Mutation, Nuclear Proteins, Pancreatic Neoplasms, Gene Expression Regulation, Neoplastic, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Proliferation, Mice, Histone Demethylases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
