ArticleCellular signalling2017
Reduced FAK-STAT3 signaling contributes to ER stress-induced mitochondrial dysfunction and death in endothelial cells.
Article in Cellular signalling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- STAT-Mediated Mitochondrial Regulation in Cardiovascular Diseases: Mechanistic Insights and STAT3-Focused Therapeutic Strategies.Biomolecules · 2026Review
- The focal adhesion kinases regulate leptin action and the weight reducing effect of HDAC6 inhibition.Nature communications · 2026Article
- Research advances on the role of programmed endothelial cell death in sepsis.Cell death discovery · 2025Review
- VEGF-B is a novel mediator of ER stress which induces cardiac angiogenesis via RGD-binding integrins independent of VEGFR1/NRP activities.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- STAT3 phosphorylation at Tyr705 affects DRP1 (dynamin-related protein 1) controlled-mitochondrial fission during the development of apoptotic-resistance in pulmonary arterial endothelial cells.Genes & genomics · 2024Article
- The crosstalk between mitochondrial quality control and metal-dependent cell death.Cell death & disease · 2024Review
- Survivin as a mediator of stiffness-induced cell cycle progression and proliferation of vascular smooth muscle cells.APL bioengineering · 2023Article
- Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis.Translational neurodegeneration · 2023Review
- PFKFB3 works on the FAK-STAT3-SOX2 axis to regulate the stemness in MPM.British journal of cancer · 2022Article
- Interplay between ZnInternational journal of molecular sciences · 2022Review
- PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD.Cell communication and signaling : CCS · 2021Article
- MFG-E8 Maintains Cellular Homeostasis by Suppressing Endoplasmic Reticulum Stress in Pancreatic Exocrine Acinar Cells.Frontiers in cell and developmental biology · 2021Article
- Microglial Activation Is Associated With Vasoprotection in a Rat Model of Inflammatory Retinal Vasoregression.Frontiers in physiology · 2021Article
- NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway.Redox biology · 2020Article
- JANEX-1 improves acute pulmonary embolism through VEGF and FAK in pulmonary artery smooth muscle cells.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Yap-Hippo pathway regulates cerebral hypoxia-reoxygenation injury in neuroblastoma N2a cells via inhibiting ROCK1/F-actin/mitochondrial fission pathways.Acta neurologica Belgica · 2020Article
- FAK activates AKT-mTOR signaling to promote the growth and progression of MMTV-Wnt1-driven basal-like mammary tumors.Breast cancer research : BCR · 2020Article
- CCR4‑NOT transcription complex subunit 2 regulates TRAIL sensitivity in non‑small‑cell lung cancer cells via the STAT3 pathway.International journal of molecular medicine · 2020Article
- Unfolded Protein Response supports endothelial barrier function.Biochimie · 2019Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Excessive endoplasmic reticulum (ER) stress leads to cell loss in many diseases, e.g., contributing to endothelial cell loss after spinal cord injury. Here, we determined whether ER stress-induced mitochondrial dysfunction could be explained by interruption of the focal adhesion kinase (FAK)-mitochondrial STAT3 pathway we recently discovered. ER stress was induced in brain-derived mouse bEnd5 endothelial cells by thapsigargin or tunicamycin and caused apoptotic cell death over a 72h period. In concert, ER stress caused mitochondrial dysfunction as shown by reduced bioenergetic function, loss of mitochondrial membrane potential and increased mitophagy. ER stress caused a reduction in mitochondrial phosphorylated S727-STAT3, known to be important for maintaining mitochondrial function. Normal activation or phosphorylation of the upstream cytoplasmic FAK was also reduced, through mechanisms that involve tyrosine phosphatases and calcium signaling, as shown by pharmacological inhibitors, bisperoxovanadium (bpV) and 2-aminoethoxydiphenylborane (APB), respectively. APB mitigated the reduction in FAK and STAT3 phosphorylation, and improved endothelial cell survival caused by ER stress. Transfection of cells rendered null for STAT3 using CRISPR technology with STAT3 mutants confirmed the specific involvement of S727-STAT3 inhibition in ER stress-mediated cell loss. These data suggest that loss of FAK signaling during ER stress causes mitochondrial dysfunction by reducing the protective effects of mitochondrial STAT3, leading to endothelial cell death. We propose that stimulation of the FAK-STAT3 pathway is a novel therapeutic approach against pathological ER stress.
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Registered trials
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