Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence
Open accessAbstract
Pancreatic acinar cells of adult mice (≥P60) are resistant to transformation by some of the most robust oncogenic insults including expression of K-Ras oncogenes and loss of p16Ink4a/p19Arf or Trp53 tumor suppressors. Yet, these acinar cells yield pancreatic intraepithelial neoplasias (mPanIN) and ductal adenocarcinomas (mPDAC) if exposed to limited bouts of non-acute pancreatitis, providing they harbor K-Ras oncogenes. Pancreatitis contributes to tumor progression by abrogating the senescence barrier characteristic of low-grade mPanINs. Attenuation of pancreatitis-induced inflammation also accelerates tissue repair and thwarts mPanIN expansion. Patients with chronic pancreatitis display senescent PanINs, providing they have received antiinflammatory drugs. These results support the concept that antiinflammatory treatment of people diagnosed with pancreatitis may reduce their risk of developing PDAC.
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Tumor development in adult mice can be greatly accelerated by chemically induced pancreatitis.
“Tumor development in adult mice, however, can be greatly accelerated by chemically induced pancreatitis.”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [81]
Inflammatory signaling is likely to play a critical role in pancreatic cancer development.
“Thus, inflammatory signaling is likely to play a critical role in pancreatic cancer development (80, 81).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [81]
Adult-onset activation of Kras-G12V in pancreatic acinar cells results in a low frequency of PanIN and resistance to transformation, partly through oncogene-induced senescence.
“pancreatic acinar cells, in which Kras-G12V is activated during adulthood, exhibit a low frequency of PanIN development and resistance to transformation, at least in part due to OIS 118”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [118]
Episodic pancreatitis induced by caerulein inhibits the OIS program and facilitates malignant transformation in the Kras-G12V pancreatic model.
“episodic pancreatitis induced by caerulein, a decapeptide analog of the gastrointestinal peptide hormone cholecystokinin, inhibited the OIS program, thus facilitating malignant transformation in this model 118”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [118]
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- Authors
- Guerra, C., Collado, M., Navas, C., Schuhmacher, A. J., Hernández-Porras, I., Cañamero, M., Rodriguez-Justo, M., Serrano, M., & Barbacid, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Corresponding author
- Guerra, Carmen
- Barbacid, Mariano
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 19
- Issue
- 6
- Pages
- 728-739
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4890723
- OpenAlex
- W1965887568
- Cited by
- 516
- References
- 40
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 31 · 2023: 40 · 2022: 22 · 2021: 44 · 2020: 36 · 2019: 41 · 2018: 27 · 2017: 36 · 2016: 22 · 2015: 37 · 2014: 65 · 2013: 38 · 2012: 33
- FWCI
- 22.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 813 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- European Research Council (ERC-AG/250297-RAS AHEAD)
- Ministerio de Ciencia e Innovación (CSD2007-00017, SAF2006-11773)
- INCLIVA Instituto de Investigación Sanitaria (ERC-AG/233270, GR/SAL/0349/2004, PI042124, SAF2008-02959)
- Fundación Mutua Madrileña
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- pancreatitis, pancreatic cancer, oncogene-induced senescence, inflammation, pancreatic intraepithelial neoplasia, K-ras oncogene, chronic pancreatitis, anti-inflammatory agents, tissue repair, tumor progression, p16INK4a, Trp53, pancreatic ductal adenocarcinoma
- MeSH terms
- Adenocarcinoma, Animals, Anti-Inflammatory Agents, Cell Transformation, Neoplastic, Humans, Pancreatic Neoplasms, Pancreatitis, Genes, ras, Genes, p53, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Carcinoma, Pancreatic Ductal, Pancreas, Exocrine, Mice
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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.
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