ArticlePLoS genetics2008
Novel roles for MLH3 deficiency and TLE6-like amplification in DNA mismatch repair-deficient gastrointestinal tumorigenesis and progression.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
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- Screening and Management of Lynch Syndrome: The Chinese Experience.Clinics in colon and rectal surgery · 2023Review
- Mutation Profile via Next-Generation Sequencing in Patients with Colorectal Adenocarcinoma and Its Clinicopathological Correlation.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Review
- A novel TLE6 mutation, c.541+1G>A, identified using whole-exome sequencing in a Chinese family with female infertility.Molecular genetics & genomic medicine · 2021Article
- Knockout of the Transducin-Like Enhancer of Split 6 Gene Affects the Proliferation and Cell Cycle Process of Mouse Spermatogonia.International journal of molecular sciences · 2020Article
- Review
- Somatic genetic aberrations in benign breast disease and the risk of subsequent breast cancer.NPJ breast cancer · 2020Article
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- Alternative splicing within the Wnt signaling pathway: role in cancer development.Cellular oncology (Dordrecht, Netherlands) · 2016Review
- Animal models of gastrointestinal and liver diseases. New mouse models for studying dietary prevention of colorectal cancer.American journal of physiology. Gastrointestinal and liver physiology · 2014Review
- Article
- Pharmacological inhibition of polycomb repressive complex-2 activity induces apoptosis in human colon cancer stem cells.Experimental cell research · 2013Article
- Animal models of colorectal cancer.Cancer metastasis reviews · 2013Review
- Article
- miR-23a promotes the transition from indolent to invasive colorectal cancer.Cancer discovery · 2012Article
- Mouse models of inherited cancer syndromes.Hematology/oncology clinics of North America · 2010Review
- Msh6 protects mature B cells from lymphoma by preserving genomic stability.The American journal of pathology · 2010Article
- Review
- Epigenetic repression of DNA mismatch repair by inflammation and hypoxia in inflammatory bowel disease-associated colorectal cancer.Cancer research · 2009Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
DNA mismatch repair suppresses gastrointestinal tumorgenesis. Four mammalian E. coli MutL homologues heterodimerize to form three distinct complexes: MLH1/PMS2, MLH1/MLH3, and MLH1/PMS1. To understand the mechanistic contributions of MLH3 and PMS2 in gastrointestinal tumor suppression, we generated Mlh3(-/-);Apc(1638N) and Mlh3(-/-);Pms2(-/-);Apc(1638N) (MPA) mice. Mlh3 nullizygosity significantly increased Apc frameshift mutations and tumor multiplicity. Combined Mlh3;Pms2 nullizygosity further increased Apc base-substitution mutations. The spectrum of MPA tumor mutations was distinct from that observed in Mlh1(-/-);Apc(1638N) mice, implicating the first potential role for MLH1/PMS1 in tumor suppression. Because Mlh3;Pms2 deficiency also increased gastrointestinal tumor progression, we used array-CGH to identify a recurrent tumor amplicon. This amplicon contained a previously uncharacterized Transducin enhancer of Split (Tle) family gene, Tle6-like. Expression of Tle6-like, or the similar human TLE6D splice isoform in colon cancer cells increased cell proliferation, colony-formation, cell migration, and xenograft tumorgenicity. Tle6-like;TLE6D directly interact with the gastrointestinal tumor suppressor RUNX3 and antagonize RUNX3 target transactivation. TLE6D is recurrently overexpressed in human colorectal cancers and TLE6D expression correlates with RUNX3 expression. Collectively, these findings provide important insights into the molecular mechanisms of individual MutL homologue tumor suppression and demonstrate an association between TLE mediated antagonism of RUNX3 and accelerated human colorectal cancer progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.