ArticleProceedings of the National Academy of Sciences of the United States of America2014
β-Catenin induces T-cell transformation by promoting genomic instability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 65 citations in OpenAlex.
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- CLOCK is an Epigenetic Integrator of Circadian Rhythm and T Cell Immunity.Research square · 2026Article
- A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development.Nature immunology · 2024Article
- Stabilization of β-Catenin Directs HEB to Limit Thymic Selection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The multifaceted roles of TCF1 in innate and adaptive lymphocytes.Advances in immunology · 2024Review
- Effects of native and particulate polyphenols on DNA damage and cell viability after UV-C exposure.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- β-Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T-cell acute lymphoblastic leukemia.EMBO molecular medicine · 2023Article
- Tcf-1 promotes genomic instability and T cell transformation in response to aberrant β-catenin activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors.Nature immunology · 2022Article
- A preclinical model of peripheral T-cell lymphoma GATA3 reveals DNA damage response pathway vulnerability.EMBO molecular medicine · 2022Article
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- LMO2 is essential to maintain the ability of progenitors to differentiate into T-cell lineage in mice.eLife · 2021Article
- FZD6 triggers Wnt-signalling driven by WNT10BHematological oncology · 2021Article
- CtBP1/2 differentially regulate genomic stability and DNA repair pathway in high-grade serous ovarian cancer cell.Oncogenesis · 2021Article
- Article
- Wnt-β-catenin activation epigenetically reprograms TNature immunology · 2021Article
- Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands.Nature immunology · 2021Article
- Stable Epigenetic Programming of Effector and Central Memory CD4 T Cells Occurs Within 7 Days of Antigen ExposureFrontiers in immunology · 2021Article
- PTEN in Regulating Hematopoiesis and Leukemogenesis.Cold Spring Harbor perspectives in medicine · 2020Review
- Dynamic regulation of chromatin organizer SATB1 via TCR-induced alternative promoter switch during T-cell development.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Deregulated activation of β-catenin in cancer has been correlated with genomic instability. During thymocyte development, β-catenin activates transcription in partnership with T-cell-specific transcription factor 1 (Tcf-1). We previously reported that targeted activation of β-catenin in thymocytes (CAT mice) induces lymphomas that depend on recombination activating gene (RAG) and myelocytomatosis oncogene (Myc) activities. Here we show that these lymphomas have recurring Tcra/Myc translocations that resulted from illegitimate RAG recombination events and resembled oncogenic translocations previously described in human T-ALL. We therefore used the CAT animal model to obtain mechanistic insights into the transformation process. ChIP-seq analysis uncovered a link between Tcf-1 and RAG2 showing that the two proteins shared binding sites marked by trimethylated histone-3 lysine-4 (H3K4me3) throughout the genome, including near the translocation sites. Pretransformed CAT thymocytes had increased DNA damage at the translocating loci and showed altered repair of RAG-induced DNA double strand breaks. These cells were able to survive despite DNA damage because activated β-catenin promoted an antiapoptosis gene expression profile. Thus, activated β-catenin promotes genomic instability that leads to T-cell lymphomas as a consequence of altered double strand break repair and increased survival of thymocytes with damaged DNA.
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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.