Ma Qingxia, Song Jingyi, Ma Hailong, Gao Kaixuan, Yang Yuecheng, He Ningning
School of Basic Medical Sciences, Qingdao University Qingdao, China.
School of Electrical Engineering and Automation, Qilu University of Technology (Shandong Academy of Science) Jinan, China.
Int J Clin Exp Pathol. 2019 Jan 1;12(1):182-189. eCollection 2019.
Growth factor receptor bound protein 2 (Grb2) is known to be an adaptor protein that provides a critical link between cell surface growth factor receptors and the MAPK signaling. It was shown that high expression of Grb2 enhances cancer cells proliferation, invasion and malignant transformation.
In this study, we aimed to systemically understand the function of Grb2 in cancer.
The expression of Grb2 in different cancer cell lines was examined from a publicly available database and we chose two cancer cell lines highly expressing Grb2 to investigate the role of Grb2. To systemically understand the function of Grb2 in cancer cells, proteomic profiles also were analyzed.
The results suggested that downregulation of Grb2 reduced cell proliferation in Hela cells and Jurkat cells. In addition, knockdown of Grb2 reduced the expression of ITGA1 and inhibited the phosphorylation of ERK. Intriguingly, simultaneous inhibition of Grb2 and ITGA1 resulted in a greater inhibition of phosphorylated ERK than either inhibition of Grb2 or ITGA1, and thus triggered marked apoptosis in Hela cells and Jurkat cells. These results suggest a synergistic anticancer effect of Grb2 and ITGA1 mediated by the ERK pathway in cancer cells highly expressing Grb2. In conclusion, we provided evidence that inhibition of Grb2 and ITGA1 might be an attractive target for therapeutic intervention against the cancer growth of cancers with high Grb2 expression.
已知生长因子受体结合蛋白2（Grb2）是一种衔接蛋白，在细胞表面生长因子受体与丝裂原活化蛋白激酶（MAPK）信号传导之间起关键连接作用。研究表明，Grb2的高表达会增强癌细胞的增殖、侵袭及恶性转化。
在本研究中，我们旨在全面了解Grb2在癌症中的功能。
从一个公开数据库中检测Grb2在不同癌细胞系中的表达情况，并选择两个高表达Grb2的癌细胞系来研究Grb2的作用。为全面了解Grb2在癌细胞中的功能，还分析了蛋白质组学图谱。
结果表明，Grb2表达下调会降低HeLa细胞和Jurkat细胞的增殖。此外，敲低Grb2会降低整合素α1（ITGA1）的表达并抑制细胞外信号调节激酶（ERK）的磷酸化。有趣的是，同时抑制Grb2和ITGA1对磷酸化ERK的抑制作用比单独抑制Grb2或ITGA1更强，从而在HeLa细胞和Jurkat细胞中引发明显的细胞凋亡。这些结果表明，在高表达Grb2的癌细胞中，Grb2和ITGA1通过ERK途径介导协同抗癌作用。总之，我们提供的证据表明，抑制Grb2和ITGA1可能是针对高表达Grb2癌症的生长进行治疗干预的一个有吸引力的靶点。
