- Integration of CiNii Books functions for fiscal year 2025 has completed
- Trial version of CiNii Research Knowledge Graph Search feature is available on CiNii Labs
- 【Updated on November 26, 2025】Regarding the recording of “Research Data” and “Evidence Data”
- Start the collection of all publicly IRDB content
- Incorporate Research Data from KAKEN
LIG4 mediates Wnt signalling-induced radioresistance
Bibliographic Information
- Published
- 2016-03-24
- Resource Type
- journal article
- Rights Information
-
- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
-
- 10.1038/ncomms10994
- Publisher
- Springer Science and Business Media LLC
Description
<jats:title>Abstract</jats:title><jats:p>Despite the implication of Wnt signalling in radioresistance, the underlying mechanisms are unknown. Here we find that high Wnt signalling is associated with radioresistance in colorectal cancer (CRC) cells and intestinal stem cells (ISCs). We find that <jats:italic>LIG4</jats:italic>, a DNA ligase in DNA double-strand break repair, is a direct target of β-catenin. Wnt signalling enhances non-homologous end-joining repair in CRC, which is mediated by <jats:italic>LIG4</jats:italic> transactivated by β-catenin. During radiation-induced intestinal regeneration, LIG4 mainly expressed in the crypts is conditionally upregulated in ISCs, accompanied by Wnt/β-catenin signalling activation. Importantly, among the DNA repair genes, LIG4 is highly upregulated in human CRC cells, in correlation with β-catenin hyperactivation. Furthermore, blocking LIG4 sensitizes CRC cells to radiation. Our results reveal the molecular mechanism of Wnt signalling-induced radioresistance in CRC and ISCs, and further unveils the unexpected convergence between Wnt signalling and DNA repair pathways in tumorigenesis and tissue regeneration.</jats:p>
Journal
-
- Nature Communications
-
Nature Communications 7 (1), 2016-03-24
Springer Science and Business Media LLC
- Tweet
Keywords
- DNA End-Joining Repair
- DNA Repair
- Regenerative Medicine
- Radiation Tolerance
- Animals, Genetically Modified
- Double-Stranded
- DNA Ligase ATP
- Mice
- 2.1 Biological and endogenous factors
- DNA Breaks, Double-Stranded
- Aetiology
- Intestinal Mucosa
- Telomerase
- Wnt Signaling Pathway
- beta Catenin
- Cancer
- Tumor
- Reverse Transcriptase Polymerase Chain Reaction
- Stem Cells
- Q
- Immunohistochemistry
- Colo-Rectal Cancer
- Gene Expression Regulation, Neoplastic
- Intestines
- Stem Cell Research - Nonembryonic - Non-Human
- Colorectal Neoplasms
- Transcriptional Activation
- DNA Ligases
- Cell Survival
- Science
- Clinical Sciences
- Genetically Modified
- Article
- Cell Line
- Cell Line, Tumor
- Animals
- Humans
- Computer Simulation
- Cell Proliferation
- Neoplastic
- Biomedical and Clinical Sciences
- Gene Expression Profiling
- DNA Breaks
- Stem Cell Research
- Gene Expression Regulation
- Digestive Diseases
Details 詳細情報について
-
- CRID
- 1360567183378808960
-
- ISSN
- 20411723
-
- PubMed
- 27009971
-
- Article Type
- journal article
-
- Data Source
-
- Crossref
- KAKEN
- OpenAIRE
