The Integrin α3β1 Signaling in the Regulation of the SK-Mel-147 Melanoma Cell Senescence

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2022-08-15 DOI:10.1134/S1990750822030088

G. E. Morozevich, N. I. Kozlova, N. M. Gevorkian, A. E. Berman

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Abstract—

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.

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整合素α3β1信号在SK-Mel-147黑色素瘤细胞衰老中的调控作用

摘要利用人SK-Mel-147黑色素瘤细胞系模型，发现通过α3特异性shRNA转导细胞阻断整合素α3β1的表达不影响其增殖，但显著增加了SA-β- gal阳性细胞的比例，这是细胞衰老的表型特征。这些变化伴随着Akt和mTOR蛋白激酶活性以及p53和p21肿瘤抑制因子表达的显著增加。mTORC1的药理抑制减少了α3β1缺失的SK-Mel-147细胞群中SA-β- gal阳性细胞的数量。基于我们最近关于Akt亚型在α2β1受体缺失引起的SK-Mel-147细胞衰老调控中的非规范功能的数据，我们研究了Akt亚型在α3β1敲低诱导的衰老中的作用。可见，在α3β1下调的细胞群中，抑制Akt1使SA-β-Gal阳性细胞数量减少到对照细胞群的水平，而抑制Akt2则无明显作用。结果表明:(1)层粘连蛋白特异性整合素α3β1与胶原特异性受体α2β1一样，参与肿瘤细胞的抗衰老作用;(ii) α3β1抑制诱导的衰老是基于Akt1亚型非规范功能的信号机制。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.