Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation
Abstract
:1. Introduction
2. Androgen and Other Non-Peptide Hormones Act via Different Receptors to Induce Proliferation of Human Breast Cancer Cells
3. Membrane Androgen Receptors
4. Integrin αvβ3 as a Receptor for DHT
5. Androgens and Breast Cancer Cell Proliferation
6. Integrin αvβ3 as a Receptor for Resveratrol
6.1. Resveratrol-Induced Apoptosis Signal Transduction Pathways: ERK1/2 and AMPK
6.2. Resveratrol-Induced Nuclear COX-2
6.3. Other Mechanisms Involved in Resveratrol-Induced Anti-Proliferation in Breast Cancers
7. Interaction of Resveratrol and DHT
8. Effect of DHT and Resveratrol on Metastasis
9. Integrin αvβ3 and Metastasis
10. VEGF and Metastasis
11. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ACTN4 | Actin-binding protein, actinin α 4 |
AMPK | AMP-activated protein kinase |
AMPKK | AMP-activated protein kinase kinase |
7α-APTADD | 7α (4′-amino) phenylthio-1,4-androstadiene-3,17-dione |
AR | Androgen receptor |
BRCA1 | Breast cancer 1 gene |
Cav-1 | Caveolin-1 |
COX-2 | Cyclooxygenase-2 |
CYP1A1 | Cytochrome P450-1A1 |
DHEAS | Dehydroepiandrosterone sulfate |
DHT | Dihydrotestosterone |
E1 | Estrone |
E1S | Estrone sulfate |
EGFR | Epidermal growth factor receptor |
ER | Estrogen receptor |
ERK1/2 | Extracellular signal-regulated kinases |
FAK | Focal adhesion kinase |
HER2 | Human epidermal growth factor receptor 2 |
17β-HSD1 | 17β-hydroxysteroid hydrogenase type 1 |
iARs | Classical intracellular androgen receptors |
LKB1 | Liver kinase B1 |
MAPK | Mitogen-activated protein kinase |
mARs | Membrane androgen receptors |
MMP-2 | Matrix metalloproteinase-2 |
PI-3K | Phosphatidylinositol-3-kinase |
PKC δ | Protein kinase C δ |
PR | Progesterone receptor |
PTEN | Phosphatase and tensin homolog |
RGD | Arg-Gly-Asp |
TSP1 | Thrombospondin-1 |
VEGF | Vascular endothelial growth factor |
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Hormone | Receptor | Functions | References |
---|---|---|---|
Estrogen | Estrogen Receptor-α (ER-α) | To form ligand-ER complex and controlling gene expression. To stimulate proliferation of breast cancer cells | [7] |
Integrin αvβ3 | NA | [8] | |
DHT | Androgen Receptor (AR) | To form ligand-AR complex and controlling gene expression To stimulate proliferation of prostate cancer cells. | [9] |
Estrogen Receptor-α (ER-α) | To stimulate proliferation of ER-positive breast cancer cells | [7] | |
Integrin αvβ3 | To stimulate proliferation of ER-negative breast cancer cells | [10] | |
Thyroid hormone | Thyroid hormone Receptor-α (TR-α) | To stimulate cancer cell growth | [11] |
Thyroid hormone Receptor-β (TR-β) | To inhibit cancer cell growth, however, mutant TR-β may activate cancer cell growth | [12] | |
Integrin αvβ3 | To stimulate cancer cell growth | [13] |
Resveratrol | DHT | |
---|---|---|
Binding Site | Integrin αvβ3 | Integrin αvβ3/ER-α/AR |
ERK1/2 | ↑ | ↑ |
PI-3K | ↓ | ↑ |
AKT | ↓ | ↑ |
PTEN | ↑ | ↓ |
Resveratrol | DHT | |
---|---|---|
Integrin | β3 ↑ | α2β1 ↓ |
EGFR | ↓ | ↑ |
VEGFR | ─ | ↑ |
VEGF | ↓ | ↑ |
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Ho, Y.; Li, Z.-L.; Shih, Y.-J.; Chen, Y.-R.; Wang, K.; Whang-Peng, J.; Lin, H.-Y.; Davis, P.J. Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation. Int. J. Mol. Sci. 2020, 21, 2906. https://doi.org/10.3390/ijms21082906
Ho Y, Li Z-L, Shih Y-J, Chen Y-R, Wang K, Whang-Peng J, Lin H-Y, Davis PJ. Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation. International Journal of Molecular Sciences. 2020; 21(8):2906. https://doi.org/10.3390/ijms21082906
Chicago/Turabian StyleHo, Yih, Zi-Lin Li, Ya-Jung Shih, Yi-Ru Chen, Kuan Wang, Jacqueline Whang-Peng, Hung-Yun Lin, and Paul J. Davis. 2020. "Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation" International Journal of Molecular Sciences 21, no. 8: 2906. https://doi.org/10.3390/ijms21082906