ArticleNature cell biology2021
LKB1 inactivation modulates chromatin accessibility to drive metastatic progression.
Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- LIF-Induced Tumor Plasticity Establishes an Immunosuppressive Myeloid Niche in LKB1-Mutant Lung Cancer.Cancer discovery · 2026Article
- YEATS2 promotes DNA repair and induces anoikis resistance by enhancing chromatin accessibility to drive prostate cancer metastasis.Oncogene · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Brain tumor detection based on transcription regulation features identified from public cerebrospinal fluid cell-free DNA sequencing data.Translational cancer research · 2026Article
- PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- Tumor suppressors LKB1 and SMARCA4 functionally interact to regulate gene expression across diverse biological processes in lung cancer.Frontiers in cell and developmental biology · 2026Article
- Evolution of Cancer Metastases via Lineage Trans-Differentiation.Research (Washington, D.C.) · 2026Article
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Article
- Advancements in lung cancer: molecular insights, innovative therapies, and future prospects.Medical oncology (Northwood, London, England) · 2025Review
- Centrosome protein TAX1BP2 mediates STING-dependent immune response and potentiates anti-PD-1 efficacy in hepatocellular carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers.Nature communications · 2025Article
- Differences between lung adenocarcinoma and lung squamous cell carcinoma: Driver genes, therapeutic targets, and clinical efficacy.Genes & diseases · 2025Review
- Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinoma.Molecular cell · 2025Article
- Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.MedComm · 2025Review
- Insights into targeting LKB1 in tumorigenesis.Genes & diseases · 2025Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- SOX17 expression in ovarian clear cell carcinoma.Journal of ovarian research · 2024Article
- Liver kinase B1 (LKB1) regulates the epigenetic landscape of mouse pancreatic beta cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Metastasis is the leading cause of cancer-related deaths and enables cancer cells to compromise organ function by expanding in secondary sites. Since primary tumours and metastases often share the same constellation of driver mutations, the mechanisms that drive their distinct phenotypes are unclear. Here we show that inactivation of the frequently mutated tumour suppressor gene LKB1 (encoding liver kinase B1) has evolving effects throughout the progression of lung cancer, which leads to the differential epigenetic re-programming of early-stage primary tumours compared with late-stage metastases. By integrating genome-scale CRISPR-Cas9 screening with bulk and single-cell multi-omic analyses, we unexpectedly identify LKB1 as a master regulator of chromatin accessibility in lung adenocarcinoma primary tumours. Using an in vivo model of metastatic progression, we further show that loss of LKB1 activates the early endoderm transcription factor SOX17 in metastases and a metastatic-like sub-population of cancer cells within primary tumours. The expression of SOX17 is necessary and sufficient to drive a second wave of epigenetic changes in LKB1-deficient cells that enhances metastatic ability. Overall, our study demonstrates how the downstream effects of an individual driver mutation can change throughout cancer development, with implications for stage-specific therapeutic resistance mechanisms and the gene regulatory underpinnings of metastatic evolution.
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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.