ArticleCancer research2022
Loss of KMT5C Promotes EGFR Inhibitor Resistance in NSCLC via LINC01510-Mediated Upregulation of MET.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Metastasis-associated DNA methylation of the lncRNAs LINC01354 and LINC01510 in clear cell renal cell carcinoma.Clinical epigenetics · 2026Article
- Article
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- KMT5C-H4K20me3 drives changes in epigenetic landscape independent of H3K9me3.bioRxiv : the preprint server for biology · 2026Article
- Solasonine inhibits NSCLC malignant progression by regulating SLC7A11 ubiquitination degradation and inducing ferroptosis.Respiratory research · 2026Article
- The methylation pattern of osimertinib resistance: prospects for diagnosis and treatment of NSCLC.Frontiers in oncology · 2026Review
- Review
- Review
- Spatial Proteomic Analysis Highlights Molecular Reprogramming in Optic Nerve Invasive Retinoblastoma.Investigative ophthalmology & visual science · 2025Article
- Targeting KMT5C Suppresses Lung Cancer Progression and Enhances the Efficacy of Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Epigenetic regulatory protein chromobox family regulates multiple signalling pathways and mechanisms in cancer.Clinical epigenetics · 2025Review
- LINC01559 drives osimertinib resistance in NSCLC through a ceRNA network regulating miR-320a/IGF2BP3 axis.Frontiers in pharmacology · 2025Article
- Comprehensive review of LncRNA-mediated therapeutic resistance in non-small cell lung cancer.Cancer cell international · 2024Review
- PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.Journal of experimental & clinical cancer research : CR · 2024Article
- CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.Journal of translational medicine · 2024Article
- Review
- MET fusions are targetable genomic variants in the treatment of advanced malignancies.Cell communication and signaling : CCS · 2024Review
- Establishing a prognostic model of chromatin modulators and identifying potential drug candidates in renal clear cell patients.BMC bioinformatics · 2023Article
- CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Histone 4 lysine 20 tri-methylation: a key epigenetic regulator in chromatin structure and disease.Frontiers in genetics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
EGFR inhibitors (EGFRi) are standard-of-care treatments administered to patients with non-small cell lung cancer (NSCLC) that harbor EGFR alterations. However, development of resistance posttreatment remains a major challenge. Multiple mechanisms can promote survival of EGFRi-treated NSCLC cells, including secondary mutations in EGFR and activation of bypass tracks that circumvent the requirement for EGFR signaling. Nevertheless, the mechanisms involved in bypass signaling activation are understudied and require further elucidation. In this study, we identify that loss of an epigenetic factor, lysine methyltransferase 5C (KMT5C), drives resistance of NSCLC to multiple EGFRis, including erlotinib, gefitinib, afatinib, and osimertinib. KMT5C catalyzed trimethylation of histone H4 lysine 20 (H4K20), a modification required for gene repression and maintenance of heterochromatin. Loss of KMT5C led to upregulation of an oncogenic long noncoding RNA, LINC01510, that promoted transcription of the oncogene MET, a component of a major bypass mechanism involved in EGFRi resistance. These findings underscore the loss of KMT5C as a critical event in driving EGFRi resistance by promoting a LINC01510/MET axis, providing mechanistic insights that could help improve NSCLC treatment. SIGNIFICANCE: Dysregulation of the epigenetic modifier KMT5C can drive MET-mediated EGFRi resistance, implicating KMT5C loss as a putative biomarker of resistance and H4K20 methylation as a potential target in EGFRi-resistant lung cancer.
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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.