Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity
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View abstract on PubMed
Summary
This summary is machine-generated.Oncogenic RAS activation in breast cells drives epithelial-to-mesenchymal plasticity (EMP) and malignant transformation. This process is fueled by inflammatory cytokines from senescent cells, challenging tumor suppression roles.
Area Of Science
- Oncology
- Cell Biology
- Molecular Biology
Background
- Aberrant RAS/MAPK pathway activation in breast cancer correlates with mesenchymal and stemness traits.
- This suggests a link between RAS/MAPK signaling and epithelial-to-mesenchymal plasticity (EMP).
Purpose Of The Study
- To investigate the role of oncogenic RAS activation in promoting EMP and malignant transformation in human mammary epithelial cells.
- To elucidate the mechanisms by which RAS signaling influences cellular senescence and EMP.
Main Methods
- Utilized inducible models of human mammary epithelial cells.
- Analyzed ZEB1-dependent EMP induction by oncogenic RAS.
- Investigated the role of pro-inflammatory cytokines, IL-6 and IL-1α, secreted by senescent cells.
Main Results
- Oncogenic RAS activation promotes ZEB1-dependent EMP, crucial for malignant transformation.
- EMP is triggered by pro-inflammatory cytokines (IL-6, IL-1α) from neighboring RAS-activated senescent cells.
- Data challenge the view of senescence as solely tumor-suppressive and EMP as only a late-stage progression factor.
Conclusions
- RAS-activated mammary epithelial cells exhibit pro-tumorigenic cooperation.
- This cooperation leverages oncogene-induced senescence and EMP for cellular reprogramming and malignant transformation.
- Highlights a novel pro-tumorigenic role for senescence and EMP in early breast cancer development.
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