Cited by 186Telomeres, Telomerase, and SenescenceGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

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Ink4a/Arf and Oncogene-Induced Senescence Prevent Tumor Progression during Alternative Colorectal Tumorigenesis

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Bennecke, Moritz, Kriegl, Lydia, Bajbouj, Monther, Retzlaff, Kristin, Robine, Sylvie, Jung, Andreas, Arkan, Melek C., Kirchner, Thomas, Greten, Florian R.·2010·Cancer Cell

DOI 10.1016/j.ccr.2010.06.013

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Abstract

Colonic cancers with a serrated morphology have been proposed to comprise a molecularly distinct tumor entity following an alternative pathway of genetic alterations independently of APC mutations. We demonstrate that intestinal epithelial cell specific expression of oncogenic K-ras(G12D) in mice induces serrated hyperplasia, which is characterized by p16(ink4a) overexpression and induction of senescence. Deletion of Ink4a/Arf in K-ras(G12D) expressing mice prevents senescence and leads to invasive, metastasizing carcinomas with morphological and molecular alterations comparable to human KRAS mutated serrated tumors. Thus, we suggest that oncogenic K-ras represents a key player during an alternative, serrated pathway to colorectal cancer and hence propose RAS-RAF-MEK signaling apart from APC as an additional gatekeeper in colorectal tumor development.

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Background
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Authors: Bennecke, M., Kriegl, L., Bajbouj, M., Retzlaff, K., Robine, S., Jung, A., Arkan, M. C., Kirchner, T., & Greten, F. R.
Affiliations: TUM Klinikum (DE)
Pathologisches Institut (DE)
Centre National de la Recherche Scientifique (FR)
Corresponding author: Greten, Florian R.
ORCID: Bennecke, Moritz
Robine, Sylvie
Jung, Andreas
Arkan, Melek C.
Kirchner, Thomas
Greten, Florian R.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2010-08
Volume: 18
Issue: 2
Pages: 135-146
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2010.06.013
OpenAlex: W2166189096
Cited by: 186
References: 48
Citations by year: 2026: 3 · 2025: 7 · 2024: 12 · 2023: 12 · 2022: 10 · 2021: 5 · 2020: 7 · 2019: 14 · 2018: 9 · 2017: 12 · 2016: 9 · 2015: 14 · 2014: 16 · 2013: 16 · 2012: 17
FWCI: 12.13
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1081 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords: Ink4a/Arf, oncogene-induced senescence, KRAS G12D, colorectal carcinogenesis, p16INK4a, metastatic colorectal cancer, Ras/Raf/MEK signaling, gatekeeper genes, tumor progression
MeSH terms: Animals, Cell Division, Humans, Immunohistochemistry, Mice, Inbred C57BL, Mutation, Oncogenes, Genes, ras, Colorectal Neoplasms, Signal Transduction, Cellular Senescence, Genes, APC, Disease Progression, Cyclin-Dependent Kinase Inhibitor p16, Wnt Proteins, Mice

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Ink4a/Arf and Oncogene-Induced Senescence Prevent Tumor Progression during Alternative Colorectal Tumorigenesis

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