ArticleNature cancer2022
KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming.
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Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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87citing papers in PubMed, 1 pooled it
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Applications of lung cancer organoids in precision medicine: from bench to bedside.Cell communication and signaling : CCS · 2023Pooled it
- High Endothelial Venules in Small Cell Lung Cancer: Prognostic Subtypes and Therapeutic Implications for Immunoradiotherapy.International journal of cancer · 2026Article
- Phylogenetic and phylodynamic approaches to understanding the evolution of non-small cell lung cancer using single-cell sequencing.Oncogene · 2026Article
- Plasma autoantibody profiling via PhIP-seq and machine learning for diagnosis of esophageal squamous cell carcinoma.Nature communications · 2026Observational
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- SUMOylation-Dependent Repression of BIRC7 by DNMT3a Suppresses Papillary Thyroid Carcinoma Progression.Cell biochemistry and function · 2026Article
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Loss of Kmt2c/d promotes gastric cancer and confers vulnerability to mTORC1 and PD-1 inhibition.The Journal of clinical investigation · 2026Article
- KMT2D loss drives adeno-to-squamous transition and sensitizes TKI-resistant lung cancer to AURKA inhibition.Cell death and differentiation · 2026Article
- ARID1A loss drives gastric signet ring cell carcinoma by regulating mucin production and secretion.Nature communications · 2026Article
- Histone mark remodeling in cancer: an enhancer-centered perspective.Genes & genomics · 2026Review
- Rectal metastasis from primary small-cell lung cancer: A case report and literature review.Medicine · 2026Review
- [Potential Mechanisms and Research Advances of HDAC1 in Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- DNMT3A in cancer: from epigenetic writer to oncogenic driver.Clinical epigenetics · 2026Review
- KMT2C Loss Promotes NF2-Wildtype Meningioma Progression and Ferroptosis Sensitivity via Epigenetic Repression of Hippo Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic regulation in cancer metastasis.Discover oncology · 2026Review
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Tendon Organoids Enable Functional Tendon Rejuvenation Through ALKBH5-Dependent RNA Demethylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Recapitulating lung cancer metastasisOncology reports · 2026Review
- Prognostic value of glioma-associated oncogene homolog 1 and SET domain-containing protein 2 immunohistochemical scores in locally advanced cervical cancer.Oncology letters · 2026Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
47 authors at 3 institutions in 2 countries.
Feifei Na *Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Xiangyu Pan *State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Jingyao Chen *State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Xuelan Chen *State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Manli WangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Pengliang ChiState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Liting YouDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Lanxin ZhangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Ailing ZhongState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Lei ZhaoState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Siqi DaiState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Mengsha ZhangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Yiyun WangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Bo WangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Jianan ZhengState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Yuying WangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Jing XuState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Jian WangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Baohong WuState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Mei ChenState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Hongyu LiuState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Jianxin XueDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Meijuan HuangDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Youling GongDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Jiang ZhuDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Lin ZhouDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Yan ZhangDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Min YuDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Panwen TianDepartment of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Mingyu FanLung Cancer Treatment Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Zhenghao LuDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Zhihong XueDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Yinglan ZhaoDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Hanshuo YangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Chengjian ZhaoState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Yuan WangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-6324-6134
Junhong HanState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-3371-8698
Shengyong YangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Dan XieState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0001-5388-5541
Lu ChenState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-1083-9729
Qian ZhongState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.ORCID http://orcid.org/0000-0003-1071-6996
Musheng ZengState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Scott W LoweCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5284-9650
You LuDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-1671-1408
Yu LiuDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-1193-7830
Yuquan WeiState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Chong ChenDepartment of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. chongchen@scu.edu.cn.ORCID http://orcid.org/0000-0002-6787-0495
Sichuan University · CNSun Yat-sen University · CNMemorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MHoward Hughes Medical InstituteNCI NIH HHS P30 CA008748
Abstract
Small cell lung cancer (SCLC) is notorious for its early and frequent metastases, which contribute to it as a recalcitrant malignancy. To understand the molecular mechanisms underlying SCLC metastasis, we generated SCLC mouse models with orthotopically transplanted genome-edited lung organoids and performed multiomics analyses. We found that a deficiency of KMT2C, a histone H3 lysine 4 methyltransferase frequently mutated in extensive-stage SCLC, promoted multiple-organ metastases in mice. Metastatic and KMT2C-deficient SCLC displayed both histone and DNA hypomethylation. Mechanistically, KMT2C directly regulated the expression of DNMT3A, a de novo DNA methyltransferase, through histone methylation. Forced DNMT3A expression restrained metastasis of KMT2C-deficient SCLC through repressing metastasis-promoting MEIS/HOX genes. Further, S-(5'-adenosyl)-L-methionine, the common cofactor of histone and DNA methyltransferases, inhibited SCLC metastasis. Thus, our study revealed a concerted epigenetic reprogramming of KMT2C- and DNMT3A-mediated histone and DNA hypomethylation underlying SCLC metastasis, which suggested a potential epigenetic therapeutic vulnerability.
Indexed as
DNA Methyltransferase 3AHistone-Lysine N-MethyltransferaseLung NeoplasmsSmall Cell Lung CarcinomaAnimalsDNADNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Modification MethylasesEpigenesis, GeneticHistonesMethyltransferasesMiceDNADNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Modification MethylasesDnmt3a protein, mouseHistone-Lysine N-MethyltransferaseHistonesKmt2c protein, mouseMethyltransferases
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