ArticleThe Journal of biological chemistry2018
Cell clustering mediated by the adhesion protein PVRL4 is necessary for α6β4 integrin-promoted ferroptosis resistance in matrix-detached cells.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Cell adhesion molecules as emerging regulators of ferroptosis: mechanisms and therapeutic opportunities in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Inducing ferroptosis to impede metastasis by inhibiting the calcium channel TRPC6.Cell reports · 2025Article
- Metabolic Regulation of Ferroptosis in Breast Cancer.International journal of molecular sciences · 2025Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Mechanisms of ferroptosis sensitization and resistance.Developmental cell · 2025Review
- Oxidative Metabolism as a Cause of Lipid Peroxidation in the Execution of Ferroptosis.International journal of molecular sciences · 2024Review
- The cell biology of ferroptosis.Nature reviews. Molecular cell biology · 2024Review
- Stress in the metastatic journey - the role of cell communication and clustering in breast cancer progression and treatment resistance.Disease models & mechanisms · 2024Article
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- PROM2 overexpression induces metastatic potential through epithelial-to-mesenchymal transition and ferroptosis resistance in human cancers.Clinical and translational medicine · 2024Article
- ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis.Gland surgery · 2024Article
- The clustering status of detached gastric cancer cells inhibits anoikis-induced ferroptosis to promote metastatic colonization.Cancer cell international · 2024Article
- Ferroptosis: underlying mechanisms and involvement in neurodegenerative diseases.Apoptosis : an international journal on programmed cell death · 2024Review
- In Situ Hybridization of circRNAs in Cells and Tissues through BaseScope™ Strategy.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills.Antioxidants & redox signaling · 2024Review
- Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.Journal of cellular and molecular medicine · 2024Review
- Deeper insight into ferroptosis: association with Alzheimer's, Parkinson's disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis.Redox report : communications in free radical research · 2023Review
- Emerging roles of ferroptosis-related miRNAs in tumor metastasis.Cell death discovery · 2023Review
- Reprogramming of iron metabolism confers ferroptosis resistance in ECM-detached cells.iScience · 2023Article
- Iron overload triggering ECM-mediated Hippo/YAP pathway in follicle development: a hypothetical model endowed with therapeutic implications.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid repair enzyme GSH peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the α6β4 integrin, which sustains GPX4 expression. Although these findings on ferroptosis are provocative, they differ from those in previous studies indicating that matrix-detached cells are prone to apoptosis via a process referred to as anoikis. In an effort to reconcile these discrepant findings, here we observed that matrix-detached epithelial and carcinoma cells cluster spontaneously via a mechanism that involves the cell adhesion protein PVRL4 (also known as Nectin-4). We found that this clustering process allows these cells to survive by stimulating a PVRL4/α6β4/Src signaling axis that sustains GPX4 expression and buffers against lipid peroxidation. In the absence of α6β4, PVRL4-mediated clustering induced an increase in lipid peroxidation that was sufficient for triggering ferroptosis. When the clustering was inhibited, single cells did not exhibit a significant increase in lipid peroxidation in the absence of α6β4, and they were more susceptible to apoptosis than to ferroptosis. These results indicate that ferroptosis induction depends on cell clustering in matrix-detached cells that lack α6β4 and imply that the fate of matrix-detached cells can be determined by the state of their cell-cell interactions.
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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.