Arid1a restrains Kras-dependent changes in acinar cell identity
Open accessAbstract
Mutations in members of the SWI/SNF chromatin remodeling family are common events in cancer, but the mechanisms whereby disruption of SWI/SNF components alters tumorigenesis remain poorly understood. To model the effect of loss of function mutations in the SWI/SNF subunit Arid1a in pancreatic ductal adenocarcinoma (PDAC) initiation, we directed shRNA triggered, inducible and reversible suppression of Arid1a to the mouse pancreas in the setting of oncogenic KrasG12D. Arid1a cooperates with Kras in the adult pancreas as postnatal silencing of Arid1a following sustained KrasG12D expression induces rapid and irreversible reprogramming of acinar cells into mucinous PDAC precursor lesions. In contrast, Arid1a silencing during embryogenesis, concurrent with KrasG12D activation, leads to retention of acinar cell fate. Together, our results demonstrate Arid1a as a critical modulator of Kras-dependent changes in acinar cell identity, and underscore an unanticipated influence of timing and genetic context on the effects of SWI/SNF complex alterations in epithelial tumorigenesis.
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 SWI/SNF factors Arid1a or Brg1 accelerates pancreatic tumorigenesis on a backdrop of cystic neoplasms resembling human IPMNs.
“deletion of SWI/SNF factors Arid1a or Brg1 results in the acceleration of pancreatic tumorigenesis on the backdrop of cystic neoplasms resembling human IPMNs98–100.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [98]
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 71 · Cited by 48
Research works printed but not linked: 1
- Flandez M Cendrowski J Cañamero M Salas A del Pozo N Schoonjans K Real FX 2014b Nr5a2 heterozygosity sensitises to, and cooperates with, inflammation in KRas(G12V)-driven pancreatic tumourigenesis Gut 63 647 655 10.1136/gutjnl-2012-304381 23598351 · DOI · Paper page
- Authors
- Livshits, G., Alonso-Curbelo, D., Morris, J. P., Koche, R., Saborowski, M., Wilkinson, J. E., & Lowe, S. W.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, United States
- Medizinische Hochschule Hannover (DE)
- University of Michigan (US)
- Corresponding author
- Lowe, Scott W
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-07-17
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6050044
- OpenAlex
- W2883052135
- Cited by
- 48
- References
- 71
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 9 · 2020: 8 · 2019: 10 · 2018: 3
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Lustgarten Foundation (388171, Research Investigator Award)
- National Cancer Institute (1F32CA177072-01, CA13106, Cancer Center Core Grants P30-CA008748)
- American Cancer Society (PF-13-037-01-DMC)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Keywords
- ARID1A, SWI/SNF chromatin remodeling, KRAS G12D, pancreatic ductal adenocarcinoma, pancreatic carcinogenesis, cellular reprogramming, oncogenic KRAS
- MeSH terms
- Animals, Cell Differentiation, Cell Transformation, Neoplastic, DNA-Binding Proteins, Gene Expression Regulation, Morphogenesis, Nuclear Proteins, Transcription Factors, Proto-Oncogene Proteins p21(ras), Carcinoma, Pancreatic Ductal, Mice, Acinar Cells, Carcinogenesis
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
