Cited by 144Telomeres, Telomerase, and SenescenceGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

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V600EBraf induces gastrointestinal crypt senescence and promotes tumour progression through enhanced CpG methylation of p16INK4a

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Carragher, Linda A. S., Snell, Kimberley R., Giblett, Susan M., Aldridge, Victoria S. S., Patel, Bipin, Cook, Simon J., Winton, Doug J., Marais, Richard, Pritchard, Catrin A.·2010·EMBO Molecular Medicine

DOI 10.1002/emmm.201000099PMC PMC3394506

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Abstract

The majority of human colorectal cancers (CRCs) are initiated by mutations arising in the adenomatous polyposis coli (APC) tumour suppressor gene. However, a new class of non-APC mutated CRCs has been defined that have a serrated histopathology and carry the (V600E)BRAF oncogene. Here we have investigated the pathogenesis of serrated CRCs by expressing (V600E)Braf in the proliferative cells of the mouse gastrointestinal tract. We show that the oncogene drives an initial burst of Mek-dependent proliferation, leading to the formation of hyperplastic crypts. This is associated with β-catenin nuclear localization by a mechanism involving Mapk/Erk kinase (Mek)-dependent, Akt-independent phosphorylation of Gsk3β. However, hyperplastic crypts remain dormant for prolonged periods due to the induction of crypt senescence accompanied by upregulation of senescence-associated β-galactosidase and p16(Ink4a). We show that tumour progression is associated with down-regulation of p16(Ink4a) through enhanced CpG methylation of exon 1 and knockout of Cdkn2a confirms this gene is a barrier to tumour progression. Our studies identify (V600E)BRAF as an early genetic driver mutation in serrated CRCs and indicate that, unlike APC-mutated cancers, this subtype arises by the bypassing of a (V600E)Braf driven oncogene-induced senescence programme.

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Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
Self-citation
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160
Stem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium
van der Flier, L. G., & Clevers, H. C. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163145 · Cited by 1,994
CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
Weisenberger, D. J., Siegmund, K. D., Campan, M., Young, J. P., Long, T. I., Faasse, M. A., Kang, G. H., Widschwendter, M., Weener, D., Buchanan, D. D., et al. (2006) · Nature Genetics · doi:10.1038/ng1834 · Cited by 1,990
High frequency of BRAF mutations in nevi
Pollock, P. M., Harper, U. L., Hansen, K. S., Yudt, L. M., Stark, M., Robbins, C. M., Moses, T. Y., Hostetter, G., Wagner, U., Kakareka, J., et al. (2003) · Nature Genetics · doi:10.1038/ng1054 · Cited by 1,730
Role of the INK4a Locus in Tumor Suppression and Cell Mortality
Serrano, M., Lee, H.-W., Chin, L., Cordon-Cardo, C., Beach, D., & DePinho, R. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81079-x · Cited by 1,585
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482
GSK3 takes centre stage more than 20 years after its discovery
FRAME, S., & COHEN, P. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590001 · Cited by 1,433
Classification of colorectal cancer based on correlation of clinical, morphological and molecular features
Jass, J. R. (2006) · Histopathology · doi:10.1111/j.1365-2559.2006.02549.x · Cited by 1,416

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Tong, K., Kothari, O. A., Haro, K. S., Panda, A., Bandari, M., Carrick, J. N., Hur, J., Zhang, L., Chan, C. S., Xing, J., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01997-x · Cited by 28
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Serrated polyps: critical precursors to colorectal cancer
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Kamata, T., & Pritchard, C. A. (2011) · Europe PMC (PubMed Central) · Cited by 23
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Authors: Carragher, L. A. S., Snell, K. R., Giblett, S. M., Aldridge, V. S. S., Patel, B., Cook, S. J., Winton, D. J., Marais, R., & Pritchard, C. A.
Affiliations: University of Leicester (GB)
Babraham Institute (GB)
Institute of Cancer Research (GB)
Corresponding author: Pritchard, Catrin A.
ORCID: Cook, Simon J.
Marais, Richard
Pritchard, Catrin A.
Venue: EMBO Molecular Medicine
Publisher: Springer Science and Business Media LLC
Published: 2010-10-13
Volume: 2
Issue: 11
Pages: 458-471
ISSN: 1757-4676 (ISSN-L)
1757-4684
DOI: 10.1002/emmm.201000099
PMC: PMC3394506
OpenAlex: W2118133069
Cited by: 144
References: 52
Citations by year: 2026: 5 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 9 · 2019: 10 · 2018: 11 · 2017: 7 · 2016: 11 · 2015: 10 · 2014: 12 · 2013: 17 · 2012: 10
FWCI: 8.01
Type: journal article
Language: en
Open access: gold
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: EMBO Molecular Medicine (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Figshare (submittedVersion, cc-by)
Leicester Research Archive (University of Leicester) (submittedVersion)
Funders: Hope Against Cancer
Cancer Research UK (C1362/A6969)
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: p16INK4a, CpG methylation, CDKN2A, oncogene-induced senescence, MEK/ERK signaling, GSK3β phosphorylation, β-catenin nuclear localization, tumor progression
MeSH terms: Glycogen Synthase Kinase 3 beta, Aging, Animals, Cell Nucleus, Hyperplasia, Colorectal Neoplasms, Up-Regulation, DNA Methylation, Cyclin-Dependent Kinase Inhibitor p16, Amino Acid Substitution, Mutation, Missense, Gene Expression Profiling, Glycogen Synthase Kinase 3, Gastrointestinal Tract, Proto-Oncogene Proteins B-raf, beta Catenin, Mice

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V600EBraf induces gastrointestinal crypt senescence and promotes tumour progression through enhanced CpG methylation of p16INK4a

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