ArticleCell discovery2022
The chromatin remodeler CHD6 promotes colorectal cancer development by regulating TMEM65-mediated mitochondrial dynamics via EGF and Wnt signaling.
Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed.
- CHD6 promotes triple-negative breast cancer progression and is associated with PI3K/AKT and MAPK pathways.International journal of clinical oncology · 2026Article
- Role of CHD chromatin remodelers in heart development.World journal of pediatrics : WJP · 2026Review
- Targeting HIF-1α promotes ferroptosis and boosts antitumor immunity in MSS colorectal cancer.Redox biology · 2026Article
- Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Advances in mitochondrial-targeted colorectal cancer therapy: Mechanistic insights and clinical translation.iScience · 2026Review
- Research progress on TMEM proteins in cancer progression and chemoresistance (Review).International journal of molecular medicine · 2025Review
- Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy.Annals of medicine · 2025Review
- The integration of single-cell and metabolomics reveals the increase of oxidative phosphorylation during the liver metastasis of colorectal cancer.Cancer & metabolism · 2025Article
- MYC/TET3-Regulated TMEM65 Activates OXPHOS-SERPINB3 Pathway to Promote Progression and Cisplatin Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations.International journal of molecular sciences · 2025Article
- LncRNA HOTTIP modulated by Hedgehog signaling drives colorectal cancer progression by promoting HUWE1-mediated ubiquitin‒proteasome degradation of p53.Cell death & disease · 2025Article
- Regulatory effect of Wnt signaling on mitochondria in cancer: from mechanism to therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Knockout of the sulfide: quinone oxidoreductase SQR reduces growth of HCT116 tumor xenograft.Redox biology · 2025Article
- Mitochondrial PGAM5 modulates methionine metabolism and feather follicle development by targeting Wnt/β-catenin signaling pathway in broiler chickens.Journal of animal science and biotechnology · 2025Article
- The Lyn/RUVBL1 Complex Promotes Colorectal Cancer Liver Metastasis by Regulating Arachidonic Acid Metabolism Through Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chromatin remodeling complexes: architects influencing breast cancer progression.Frontiers in cell and developmental biology · 2025Review
- The role of PSMC4 in non-small cell lung cancer: implications for prognosis, diagnosis, and immune microenvironment modulation.Frontiers in oncology · 2025Article
- EGF-Upregulated lncRNA ESSENCE Promotes Colorectal Cancer Growth through Stabilizing CAD and Ferroptosis Defense.Research (Washington, D.C.) · 2025Article
- Review
- CHD6 eviction of promoter nucleosomes maintains housekeeping transcriptional program in prostate cancer.Molecular therapy. Nucleic acids · 2024Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Chromodomain helicase DNA binding protein (CHD) family plays critical roles in regulating gene transcription. The family is linked to cancer disease, but the family member's role in tumorigenesis remains largely unknown. Here, we report that CHD6 is highly expressed in colorectal cancer (CRC). CHD6 knockdown inhibited cancer cell proliferation, migration, invasion, and tumorigenesis. Consistently, Villin-specific Chd6 knockout in mice attenuates cancer formation in AOM/DSS model. We found that aberrant EGF signals promoted the stability of CHD6 by diminishing ubiquitin-mediated degradation. EGF signal inhibits GSK3β activity, which in turn prevents phosphodegron formation of CHD6, thereby hindering E3 ligase FBXW7-mediated CHD6 ubiquitination and degradation. CHD6's chromatin remodeler activity engages in binding Wnt signaling transcription factor TCF4 to facilitate the transcriptional expression of TMEM65, a mitochondrial inner membrane protein involved in ATP production and mitochondrial dynamics. In addition, Wnt signaling is also an upstream regulator of CHD6. CHD6 promoter contains TCF4 and β-catenin binding site, and CHD6 can be transcriptionally activated by Wnt ligand to facilitate TMEM65 transcription. Thus CHD6-TMEM65 axis can be regulated by both EGF and Wnt signaling pathways through two different mechanisms. We further illustrate that CHD6-TMEM65 axis is deregulated in cancer and that co-administration of Wnt inhibitor LGK974 and the anti-EGFR monoclonal antibody cetuximab largely restricted the growth of patient-derived xenografts of CRC. Targeting CHD6-TMEM65 axis may be effective for cancer intervention.
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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.