Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition: Insights into Cellular Mechanisms and Signaling Pathways
Abstract
:1. Introduction
2. Cigarette Smoke (CS) and Human Bronchial Epithelial Cells
2.1. Toxic Components of Cigarette Smoke
2.2. Human Bronchial Epithelial Cells
3. Evidence of Cigarette Smoke-Induced EMT
3.1. Cigarette Smoke (CS)-Induced Epithelial-to-Mesenchymal Transition (EMT)
3.2. Structural Evidence
3.3. Functional Evidence
4. Molecular Mechanisms of CS-Induced EMT
4.1. WNT/β-Catenin Signaling Pathway
4.2. TGF-β/SMAD Signaling Pathway
4.3. Hypoxia Signaling Pathway
4.4. Oxidative Stress Signaling Pathway
4.5. PI3K/Akt Pathway
4.6. Endoplasmic Reticulum (ER) Stress
4.7. NF-KB Signaling Pathway
4.8. Notch Signaling Pathway
4.9. Hedgehog Signaling Pathway
4.10. Macrophages and CS
5. Strengths and Limitations
6. Conclusions
7. Methodology
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Type of Cancer | Smoking Status | Prognostic Findings | Impact on Survival | Study |
---|---|---|---|---|
Multiple cancers | Current/former smokers | Higher incidence of second primary cancers in smokers. | Significantly reduced overall survival rates. | [6] |
Bladder cancer | Current/former smokers | Higher recurrence rates and more aggressive tumor phenotypes in smokers. | Lower disease-free survival and overall survival in smokers. | [6] |
Esophageal cancer | Current smokers | Smoking-related esophageal cancer has a higher likelihood of recurrence post-treatment. | Reduced survival and higher recurrence rates post-esophagectomy. | [10] |
Lung cancer | Current smokers | Increased risk of second primary lung cancer among smokers. | Reduced overall survival and progression-free survival. | [5] |
Non-small cell lung cancer (NSCLC) | Current smokers | Higher incidence of squamous cell carcinoma subtype among smokers. | Lower survival rates in smokers compared to nonsmokers. | [3] |
Colorectal cancer | Current/former smokers | Increased pulmonary metastasis in smokers. | Increased mortality due to liver and lung metastasis. | [7] |
Study | Type of Cell Line | Rate of CS Exposure | Downregulated Epithelial Marker | Upregulated Mesenchymal Marker |
---|---|---|---|---|
[123] | Primary HBE | 1.5% CSE for 48 h | E-cadherin | Vimentin, MMP-9 |
[85] | Primary HBEC | 5% CSE for 24 h | E-cadherin ZO-1 | Vimentin |
[81] | Immortalized 16HBE14o- | 40 μmol/L nicotine treated for 72 h | E-cadherin | α-SMA |
[100] | Immortalized 16HBE | 3% CSE for 48 h | E-cadherin | E-cadherin fibronectin, α-SMA, Collagen 1, Collagen 3 |
[66] | Immortalized 16-HBE | 5, 10 and 20% CSE for 24 h | E-cadherin | N-cadherin, α-SMA, Slug, FN1, Collagen IV |
[124] | Immortalized HBE | 0.5, 1, and 2% CSE for 24 h | E-cadherin | N-cadherin, Vimentin α -SMA |
[65] | Immortalized HBE | 1, 2, 4% CSE for 48 h | E-cadherin | N-cadherin, Vimentin, α-SMA, Snail, FoxC1 |
[55] | Primary HBE | 10% CSE for 24 and 48 h | E-cadherin ZO-1 | α-SMA, Vimentin |
[98] | Immortalized 16HBE | 2.5% CSE for 48 h | E-cadherin | α-SMA, Vimentin, MMP-9, MMP-2 |
[76] | Immortalized 16HBE | 2.5, 5% CSE for 72 h, and 5% CSE for 6 h, 12 h, 24 h, 48 h, 72 h | E-cadherin | α-SMA, Vimentin |
[77] | Immortalized BEAS-2B | 10% CSE for 48 h | E-cadherin | α-SMA |
[67] | Primary NHBE Normal human bronchial epithelial cells | 2 and 4% CSE for 7 days | E-cadherin ZO-1 | N-cadherin, Vimentin |
[68] | Immortalized BEAS-2B | 5% CSE for 5 days | E-cadherin | Vimentin, N-cadherin, α-SMA |
[56] | Immortalized BEAS-2B | 1% CSE every 24 h for 48 h | E-cadherin ZO-1 keratin 18 | Vimentin, PAI-1, Fibronectin, Snail |
[59] | Primary HBEC | 6 × 10−6 mol/L nicotine for 24 h | E-cadherin | α-SMA, Vimentin, Collagen I, MMP-9 |
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Alqithami, S.M.; Machwe, A.; Orren, D.K. Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition: Insights into Cellular Mechanisms and Signaling Pathways. Cells 2024, 13, 1453. https://doi.org/10.3390/cells13171453
Alqithami SM, Machwe A, Orren DK. Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition: Insights into Cellular Mechanisms and Signaling Pathways. Cells. 2024; 13(17):1453. https://doi.org/10.3390/cells13171453
Chicago/Turabian StyleAlqithami, Sarah Mohammed, Amrita Machwe, and David K. Orren. 2024. "Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition: Insights into Cellular Mechanisms and Signaling Pathways" Cells 13, no. 17: 1453. https://doi.org/10.3390/cells13171453