| Autor: |
Morozevich, G. E., Kozlova, N. I., Gevorkian, N. M., Berman, A. E. |
| Zdroj: |
Biochemistry (Biokhimiya). Supplemental Series B, Biomedical Chemistry; Sep2022, Vol. 16 Issue 3, p187-194, 8p |
| Abstrakt: |
Using a model of the human SK-Mel-147 melanoma cell line, it was shown that blocking the expression of integrin α3β1 by transduction of cells with α3-specific shRNA did not affect their proliferation, but sharply increased the proportion of SA-β-Gal-positive cells, a phenotypic feature of cell senescence. These changes were accompanied by a significant increase in the activity of the Akt and mTOR protein kinases and the expression of p53 and p21 oncosupressors. The pharmacological inhibition of mTORC1 reduced the number SA-β-Gal-positive cells in the SK-Mel-147 cell population depleted of α3β1. Based on our recent data on a non-canonical function of Akt isoforms in the regulation of SK-Mel-147 cell senescence caused by α2β1 receptor deficiency, we have investigated the role of Akt isoforms in senescence induced by the α3β1 knockdown. It appeared that in the cell population with downregulated α3β1, inhibition of Akt1 reduced the number SA-β-Gal positive cells to the level of control cell population, while inhibition of Akt2 had no visible effect. Our results demonstrate that: (i) the laminin-specific integrin α3β1, like the collagen-specific receptor α2β1, is involved in tumor cell protection from senescence; (ii) senescence induced by α3β1 suppression is based on a signaling mechanism employing a non-canonical function of the Akt1 isoform. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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