Cigarette smoke extract stimulates epithelial-mesenchymal transition through Src activation
Hongqiao Zhang1, Honglei Liu, Zea Borok
1Andrus Gerontology Center, Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Free Radical Biology & Medicine
|February 21, 2012
Summary
Cigarette smoke extract (CSE) induces epithelial-mesenchymal transition (EMT) in lung cells via Src kinase activation. The antioxidant N-acetylcysteine (NAC) prevents this process, suggesting a redox mechanism involving acrolein.
Area of Science:
- Cell Biology
- Toxicology
- Oncology
Background:
- Epithelial-mesenchymal transition (EMT) is crucial in lung fibrosis and cancer metastasis.
- Cigarette smoke (CS) is a major risk factor for lung cancer and promotes EMT, but the mechanism is unclear.
Purpose of the Study:
- To investigate how CS induces EMT in non-small-cell lung carcinoma (H358) cells.
- To explore the underlying molecular mechanisms of CS-induced EMT.
Main Methods:
- H358 cells were exposed to CS extract (CSE).
- Changes in EMT markers (E-cadherin, N-cadherin, vimentin) were assessed.
- The role of N-acetylcysteine (NAC), Src kinase, and acrolein was investigated.
Main Results:
- CSE decreased E-cadherin and increased N-cadherin and vimentin, indicating EMT.
- NAC treatment abrogated CSE-induced EMT markers and Src activation.
- CSE activated Src kinase, which was inhibited by PP2, and acrolein activated Src.
Conclusions:
- CSE induces EMT in lung cells through Src kinase activation.
- Redox modification, potentially involving acrolein, mediates CS-induced Src activation.
- NAC can block CS-induced EMT, highlighting its potential therapeutic role.
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