Biotechnology Institute of Ankara University, 06135, Ankara, Turkey.
Department of Medical Pharmacology, Faculty of Medicine, University of Ankara, 06230, Ankara, Turkey.
Sci Rep. 2021 Jan 15;11(1):1539. doi: 10.1038/s41598-021-80974-6.
β-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.
β- arrestins(βArrs)是细胞内信号调节蛋白。它们在一些癌症中的表达水平不同,对癌细胞功能有重要影响。一般来说,βArrs 在癌症研究中的意义来自于研究 GPCR 信号的研究。鉴于不同 GPCR 信号在癌细胞调节中的多样性,关于 βArrs 的作用不可避免地会产生矛盾的结果。我们的方法通过改变乳腺癌细胞 MDA-MB-231 和 MDA-MB-468 中 βArrs 的表达水平,研究 βArrs 对细胞功能和基因表达谱的直接影响。降低 βArr1 或 βArr2 的表达水平往往会增加细胞增殖和侵袭能力,而增加其表达水平则会抑制它们。βArrs 的过表达导致细胞周期 S 期停滞和细胞周期基因的差异表达,CDC45、BUB1、CCNB1、CCNB2、CDKN2C 的表达减少,HER3、IGF-1R 和 Snail 的表达减少。关于我们研究结果的临床相关性,与正常组织样本相比,βArr1 的低表达水平与 CDC45、BUB1、CCNB1 和 CCNB2 基因呈负相关,而与乳腺癌的预后较差呈正相关。这些结果表明,βArr1 和 βArr2 通过影响细胞周期基因以及 TNBC 细胞中的 HER3、IGF-1R 和 Snail,显著参与细胞周期和抗癌信号通路。