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Updated: Jul 25, 2025
Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Implication of integrin α5β1 in senescence of SK-Mel-147 human melanoma cells
N I Kozlova1, G E Morozevich1, N M Gevorkian1
1Institute of Biomedical Chemistry, Moscow, Russia.
Abstract:
Downregulation of α5β1 integrin in the SK-Mel-147 human melanoma culture model sharply inhibits the phenotypic manifestations of tumor progression: cell proliferation and clonal activity. This was accompanied by a 2-3-fold increase in the content of SA-β-Gal positive cells thus indicating an increase in the cellular senescence phenotype. These changes were accompanied by a significant increase in the activity of p53 and p21 tumor suppressors and components of the PI3K/Akt/mTOR/p70 signaling pathway. Pharmacological inhibition of mTORC1 reduced the content of SA-β-Gal positive cells in the population of α5β1-deficient SK-Mel-147 cells. A similar effect was observed with pharmacological and genetic inhibition of the activity of Akt1, one of the three Akt protein kinase isoenzymes; suppression of other Akt isozymes did not affect melanoma cell senescence. The results presented in this work and previously obtained indicate that α5β1 shares with other integrins of the β1 family the function of cell protection from senescence. This function is realized via regulation of the PI3K/Akt1/mTOR signaling pathway, in which Akt1 exhibits a non-canonical activity.
Insights
Inhibiting α5β1 integrin in melanoma cells halts tumor progression and increases senescence. This occurs through the PI3K/Akt1/mTOR pathway, highlighting α5β1
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Integrins are crucial for cell adhesion and signaling in cancer.
- α5β1 integrin plays a role in melanoma progression.
- Cellular senescence is a key factor in tumor suppression.
Purpose of the Study:
- To investigate the role of α5β1 integrin in melanoma progression and senescence.
- To elucidate the signaling pathways involved in α5β1 integrin-mediated melanoma cell behavior.
Main Methods:
- Utilized the SK-Mel-147 human melanoma cell culture model.
- Downregulated α5β1 integrin expression.
- Assessed cell proliferation, clonal activity, and senescence markers (SA-β-Gal).
- Analyzed the activity of p53, p21, and the PI3K/Akt/mTOR/p70 signaling pathway.
- Employed pharmacological and genetic inhibition of mTORC1 and Akt1.
Main Results:
- Downregulation of α5β1 integrin inhibited melanoma cell proliferation and clonal activity.
- A significant increase in senescence (SA-β-Gal positive cells) was observed.
- Activity of p53, p21, and the PI3K/Akt/mTOR/p70 pathway increased.
- Inhibition of mTORC1 and specifically Akt1 reduced senescence in α5β1-deficient cells.
Conclusions:
- α5β1 integrin protects melanoma cells from senescence.
- This protective function is mediated by the PI3K/Akt1/mTOR signaling pathway.
- Akt1 exhibits non-canonical activity in regulating melanoma cell senescence via α5β1 integrin.
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