ArticleMolecular biology of the cell2016
LKB1 kinase-dependent and -independent defects disrupt polarity and adhesion signaling to drive collagen remodeling during invasion.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Review
- Clusters, fingers, and singles: A mechanical landscape of tumor invasion.PLoS computational biology · 2026Article
- Intraoperative biopsy imaging of lung cancer risk.Communications medicine · 2026Article
- Targeting LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance.Trends in pharmacological sciences · 2025Review
- High PER1 expression is associated with STK11 mutation and clinical biomarkers of immunotherapy resistance in lung adenocarcinoma.Journal of cancer research and clinical oncology · 2025Article
- Truncated LKB1 nonenzymatically enhances Fas-induced apoptosis by acting as a surrogate of Smac.Cell death discovery · 2025Article
- Live-Cell Invasive Phenotyping Uncovers ALK2 as a Therapeutic Target in LKB1-Mutant Lung Cancer.Cancer research · 2024Article
- Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes.Current issues in molecular biology · 2024Review
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- Subpopulation commensalism promotes Rac1-dependent invasion of single cells via laminin-332.The Journal of cell biology · 2024Article
- Article
- Targeting focal adhesion kinase boosts immune response in KRAS/LKB1 co-mutated lung adenocarcinoma via remodeling the tumor microenvironment.Experimental hematology & oncology · 2024Article
- STK11 loss leads to YAP1-mediated transcriptional activation in human KRAS-driven lung adenocarcinoma cell lines.Cancer gene therapy · 2024Article
- Liver Kinase B1 Mediates Its Anti-Tumor Function by Binding to the N-Terminus of Malic Enzyme 3.Biomolecules & therapeutics · 2023Article
- Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells.International journal of molecular sciences · 2022Article
- Extracellular matrix in cancer progression and therapy.Medical review (2021) · 2022Review
- Liver Kinase B1 Regulates Remodeling of the Tumor Microenvironment in Triple-Negative Breast Cancer.Frontiers in molecular biosciences · 2022Article
- Functional assessment of somatic STK11 variants identified in primary human non-small cell lung cancers.Carcinogenesis · 2021Article
- STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation.Communications biology · 2020Article
- Subpopulation targeting of pyruvate dehydrogenase and GLUT1 decouples metabolic heterogeneity during collective cancer cell invasion.Nature communications · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
LKB1 is a serine/threonine kinase and a commonly mutated gene in lung adenocarcinoma. The majority of LKB1 mutations are truncations that disrupt its kinase activity and remove its C-terminal domain (CTD). Because LKB1 inactivation drives cancer metastasis in mice and leads to aberrant cell invasion in vitro, we sought to determine how compromised LKB1 function affects lung cancer cell polarity and invasion. Using three-dimensional models, we show that LKB1 kinase activity is essential for focal adhesion kinase-mediated cell adhesion and subsequent collagen remodeling but not cell polarity. Instead, cell polarity is overseen by the kinase-independent function of its CTD and more specifically its farnesylation. This occurs through a mesenchymal-amoeboid morphological switch that signals through the Rho-GTPase RhoA. These data suggest that a combination of kinase-dependent and -independent defects by LKB1 inactivation creates a uniquely invasive cell with aberrant polarity and adhesion signaling that drives invasion into the microenvironment.
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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.