ArticleThe Journal of experimental medicine2018
Ezh2 inhibition in Kras-driven lung cancer amplifies inflammation and associated vulnerabilities.
Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Dual targeting of CXCR4 and EZH2 in endometriosis.iScience · 2025Article
- Proteogenomic discovery ofScience advances · 2025Article
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.The Journal of experimental medicine · 2025Article
- A Peptide Encoded by lncRNA HOXB-AS3 Promotes Cigarette Smoke-Induced Inflammation in Bronchial Epithelial Cells via EZH2-Mediated H3K27me3 Modification.International journal of chronic obstructive pulmonary disease · 2025Article
- Review
- EZH2 represses mesenchymal genes and upholds the epithelial state of breast carcinoma cells.Cell death & disease · 2024Article
- Tumor-suppressive functions of protein lysine methyltransferases.Experimental & molecular medicine · 2023Review
- CUL4B functions as a tumor suppressor in KRAS-driven lung tumors by inhibiting the recruitment of myeloid-derived suppressor cells.Oncogene · 2023Article
- An integrated model for predicting KRAS dependency.PLoS computational biology · 2023Article
- Targeting Inflammation in Non-Small Cell Lung Cancer through Drug Repurposing.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Polycomb deficiency drives a FOXP2-high aggressive state targetable by epigenetic inhibitors.Nature communications · 2023Article
- Article
- MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response.Nature communications · 2021Article
- Inhibition of cytoplasmic EZH2 induces antitumor activity through stabilization of the DLC1 tumor suppressor protein.Nature communications · 2021Article
- Decreased PRC2 activity supports the survival of basal-like breast cancer cells to cytotoxic treatments.Cell death & disease · 2021Article
- Phenotypic Mapping of Pathologic Cross-Talk between Glioblastoma and Innate Immune Cells by Synthetic Genetic Tracing.Cancer discovery · 2021Article
- Functional antagonism of chromatin modulators regulates epithelial-mesenchymal transition.Science advances · 2021Article
- USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells.Cell reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kras-driven non-small-cell lung cancers (NSCLCs) are a leading cause of death with limited therapeutic options. Many NSCLCs exhibit high levels of Ezh2, the enzymatic subunit of polycomb repressive complex 2 (PRC2). We tested Ezh2 inhibitors as single agents or before chemotherapy in mice with orthotopic Kras-driven NSCLC grafts, which homogeneously express Ezh2. These tumors display sensitivity to EZH2 inhibition by GSK126 but also amplify an inflammatory program involving signaling through NF-κB and genes residing in PRC2-regulated chromatin. During this process, tumor cells overcome GSK126 antiproliferative effects. We identified oncogenes that may mediate progression through an in vivo RNAi screen aimed at targets of PRC2/NF-κB. An in vitro compound screening linked GSK126-driven inflammation and therapeutic vulnerability in human cells to regulation of RNA synthesis and proteostasis. Interestingly, GSK126-treated NSCLCs in vivo also showed an enhanced response to a combination of nimesulide and bortezomib. Thus, Ezh2 inhibition may restrict cell proliferation and promote defined adaptive responses. Targeting these responses potentially improves outcomes in Kras-driven NSCLCs.
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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.