Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling
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View abstract on PubMed
Summary
This summary is machine-generated.Intercellular interactions regulate ferroptosis, a cell death process implicated in cancer. E-cadherin and the NF2-Hippo pathway suppress ferroptosis in epithelial cells, while YAP activation promotes it, offering new therapeutic targets.
Area Of Science
- Cell Biology
- Cancer Research
- Molecular Mechanisms of Cell Death
Background
- Ferroptosis is an iron-dependent cell death pathway implicated in diseases like cancer and organ damage.
- Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis, protecting cells from lipid peroxidation.
- Cancer cells with mesenchymal traits are paradoxically sensitive to ferroptosis.
Purpose Of The Study
- To investigate the non-cell-autonomous regulation of ferroptosis by intercellular interactions.
- To elucidate the molecular mechanisms linking cell adhesion to ferroptosis sensitivity.
- To explore the role of the NF2-Hippo-YAP signaling axis in ferroptosis regulation.
Main Methods
- Investigated ferroptosis regulation in epithelial and non-epithelial cells.
- Utilized genetic manipulation and pharmacological inhibition of signaling pathways.
- Employed an orthotopic mouse model of malignant mesothelioma.
Main Results
- E-cadherin-mediated intercellular interactions suppress ferroptosis in epithelial cells via the NF2-Hippo pathway.
- Inhibition of the NF2-Hippo pathway activates YAP, promoting ferroptosis by upregulating ACSL4 and TFRC.
- Genetic inactivation of NF2 increased ferroptosis sensitivity in a mesothelioma mouse model.
Conclusions
- Intercellular interactions and the NF2-YAP signaling axis are critical regulators of ferroptosis.
- This mechanism explains the heightened ferroptosis sensitivity in mesenchymal cancer cells.
- NF2-YAP signaling status may predict patient response to ferroptosis-inducing therapies.
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