ArticleBMC cancer2016
The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
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- Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics.Scientific reports · 2025Article
- Exploring the Structural and Functional Consequences of Deleterious Missense Nonsynonymous SNPs in theJournal of personalized medicine · 2024Article
- Integrin β5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis and immunotherapy efficacy in gastric cancer.BMC gastroenterology · 2024Article
- ROS-mediated ITGB5 promotes tongue squamous cell carcinoma metastasis through epithelial mesenchymal transition and cell adhesion signal pathway.Journal of cancer research and clinical oncology · 2024Article
- Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the AKT/MDM2/P53 pathway.Scientific reports · 2024Article
- Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance.Frontiers in cell and developmental biology · 2024Review
- Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage.Experimental and molecular pathology · 2023Article
- Nanomedicine Strategies for Targeting Tumor Stroma.Cancers · 2023Review
- Irisin Induces Apoptosis in Metastatic Prostate Cancer Cells and Inhibits Tumor Growth In Vivo.Cancers · 2023Article
- Induction of pro-inflammatory genes by fibronectin DAMPs in three fibroblast cell lines: Role of TAK1 and MAP kinases.PloS one · 2023Article
- Preclinical Assessment of MEK Inhibitors for Malignant Peripheral Nerve Sheath Tumors Reveals Differences in Efficacy and Adaptive Response.Frontiers in oncology · 2022Article
- Fibronectin as a multiregulatory molecule crucial in tumor matrisome: from structural and functional features to clinical practice in oncology.Journal of experimental & clinical cancer research : CR · 2021Review
- Zi Shen Decoction Inhibits Growth and Metastasis of Lung Cancer via Regulating the AKT/GSK-3Oxidative medicine and cellular longevity · 2021Article
- Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway.International journal of cancer · 2020Article
- Cirsiliol Suppressed Epithelial to Mesenchymal Transition in B16F10 Malignant Melanoma Cells through Alteration of the PI3K/Akt/NF-κB Signaling Pathway.International journal of molecular sciences · 2019Article
- Multiple Interactions Between Cancer Cells and the Tumor Microenvironment Modulate TRAIL Signaling: Implications for TRAIL Receptor Targeted Therapy.Frontiers in immunology · 2019Review
- Tumor necrosis factor-related apoptosis-inducing ligand additive with Iodine-131 of inhibits non-small cell lung cancer cells through promoting apoptosis.Oncology letters · 2018Article
- Microenvironmental Signals and Biochemical Information Processing: Cooperative Determinants of Intratumoral Plasticity and Heterogeneity.Frontiers in cell and developmental biology · 2018Review
- Fibronectin Promotes the Malignancy of Glioma Stem-Like Cells Via Modulation of Cell Adhesion, Differentiation, Proliferation and Chemoresistance.Frontiers in molecular neuroscience · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFibronectin is a mechanically sensitive protein which is organized in the extracellular matrix as a network of interacting fibrils. The lung tumor stroma is enriched for fibronectin which is thought to contribute to metastasis and drug resistance. Fibronectin is an elastic, multi-modular protein made up of individually folded domains, some of which can stretch in response to increased mechanical tension. Very little is known about the relationship of fibronectin's unfolded domains to lung cancer resistance to chemotherapy. In the present study, we evaluated the impact of unfolding the first Type III domain of fibronectin (FnIII-1c) on TNF-related apoptosis inducing ligand (TRAIL) resistance.
methodsNCI-H460 non-small cell lung cancer cells were treated with FnIII-1c then assessed for TRAIL-induced apoptosis. Subsequent analysis of FnIII-1c-mediated signaling pathways was also completed. Human non-small cell lung cancer tissue sections were assessed for the expression of vitronectin by immunohistochemistry.
resultsFnIII-1c inhibited TRAIL-induced activation of caspase 8 and subsequent apoptosis in NCI-H460 lung cancer cells. FnIII-1c treatment was associated with the activation of the phosphatidylinositol-3-kinase/alpha serine/threonine kinase (PI3K/Akt) pathway and the αvβ5 integrin receptor for vitronectin, both of which were required for TRAIL resistance. Immunohistochemical staining of sections from non-small cell lung cancers showed that vitronectin was localized around blood vessels and in the tumor-stroma interface.
conclusionsUnfolding of Type III domains within the fibronectin matrix may promote TRAIL resistance through the activation of a PI3K/Akt/αvβ5 signaling axis and point to a novel mechanism by which changes in secondary structure of fibronectin contribute to cancer cell resistance to apoptosis.
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