ArticleThe Journal of biological chemistry2013
LKB1 represses focal adhesion kinase (FAK) signaling via a FAK-LKB1 complex to regulate FAK site maturation and directional persistence.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Early detection of invasive lung cancer and multiorgan metastasis by a collagen-targeted protein MRI contrast agent.Science advances · 2026Article
- Suppression of STK11 induces expansion of polymorphonuclear myeloid-derived suppressive cells and activation of immune signaling in breast cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Live-Cell Invasive Phenotyping Uncovers ALK2 as a Therapeutic Target in LKB1-Mutant Lung Cancer.Cancer research · 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
- The role of STK11/LKB1 in cancer biology: implications for ovarian tumorigenesis and progression.Frontiers in cell and developmental biology · 2024Review
- 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 alterations in the pan-cancer setting: prognostic and therapeutic implications.European journal of cancer (Oxford, England : 1990) · 2021Article
- Leflunomide Suppresses the Growth of LKB1-Inactivated Tumors in the Immune-Competent Host and Attenuates Distant Cancer Metastasis.Molecular cancer therapeutics · 2021Article
- LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway.Frontiers in physiology · 2021Article
- STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation.Communications biology · 2020Article
- LKB1 deficiency promotes proliferation and invasion of glioblastoma through activation of mTOR and focal adhesion kinase signaling pathways.American journal of cancer research · 2019Article
- Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development.Cancers · 2018Review
- Targeting adhesion signaling inJCI insight · 2017Article
- Coordinated cell motility is regulated by a combination of LKB1 farnesylation and kinase activity.Scientific reports · 2017Article
- Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer.International journal of molecular sciences · 2017Review
- Local alignment vectors reveal cancer cell-induced ECM fiber remodeling dynamics.Scientific reports · 2017Article
- AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion.Molecular biology of the cell · 2016Article
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Authors and funding
5 authors.
Funding
Abstract
Liver kinase β1 (LKB1, also known as STK11) is a serine/threonine kinase that has multiple cellular functions including the regulation of cell polarity and motility. Murine proteomic studies show that LKB1 loss causes aberrant adhesion signaling; however, the mechanistic underpinnings of this relationship are unknown. We show that cells stably depleted of LKB1 or its co-activator STRADα have increased phosphorylation of focal adhesion kinase (FAK) at Tyr(397)/Tyr(861) and enhanced adhesion to fibronectin. LKB1 associates in a complex with FAK and LKB1 accumulation at the cellular leading edge is mutually excluded from regions of activated Tyr(397)-FAK. LKB1-compromised cells lack directional persistence compared with wild-type cells, but this is restored through subsequent pharmacological FAK inhibition or depletion, showing that cell directionality is mediated through LKB1-FAK signaling. Live cell confocal imaging reveals that LKB1-compromised cells lack normal FAK site maturation and turnover, suggesting that defects in adhesion and directional persistence are caused by aberrant adhesion dynamics. Furthermore, re-expression of full-length wild-type or the LKB1 N-terminal domain repressed FAK activity, whereas the kinase domain or C-terminal domain alone did not, indicating that FAK suppression is potentially regulated through the LKB1 N-terminal domain. Based upon these results, we conclude that LKB1 serves as a FAK repressor to stabilize focal adhesion sites, and when LKB1 function is compromised, aberrant FAK signaling ensues, resulting in rapid FAK site maturation and poor directional persistence.
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