Implication of integrin α5β1 in senescence of SK-Mel-147 human melanoma cells.

Q3 Biochemistry, Genetics and Molecular Biology Biomeditsinskaya khimiya Pub Date : 2023-06-01 DOI:10.18097/PBMC20236903156
N I Kozlova, G E Morozevich, N M Gevorkian, L K Kurbatov, A E Berman
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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.

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整合素α5β1在SK-Mel-147人黑色素瘤细胞衰老中的意义。
在SK-Mel-147人黑色素瘤培养模型中下调α5β1整合素可显著抑制肿瘤进展的表型表现:细胞增殖和克隆活性。与此同时,SA-β-Gal阳性细胞的含量增加了2-3倍,从而表明细胞衰老表型增加。这些变化伴随着p53和p21肿瘤抑制因子以及PI3K/Akt/mTOR/p70信号通路组分活性的显著增加。药理抑制mTORC1可降低α5β1缺失的SK-Mel-147细胞中SA-β-Gal阳性细胞的含量。对Akt蛋白激酶三种同工酶之一的Akt1的药理和遗传抑制也有类似的效果;抑制其他Akt同工酶对黑色素瘤细胞衰老没有影响。本研究和前人的研究结果表明,α5β1与β1家族的其他整合素具有保护细胞衰老的功能。这一功能是通过调控PI3K/Akt1/mTOR信号通路实现的,其中Akt1表现出非规范活性。
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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍: The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).
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