GRK5 functions as an oncogenic factor in non-small-cell lung cancer.
GRK5 functions as an oncogenic factor in non-small-cell lung cancer.
复制标题
GRK5 作为非小细胞肺癌的致癌因子
DOI：
10.1038/s41419-018-0299-1
复制
发表时间：
2018-02-20
影响因子：
9
通讯作者：
Chen YB
中科院分区：
文献类型：
--
作者：
Jiang LP;Fan SQ;Xiong QX;Zhou YC;Yang ZZ;Li GF;Huang YC;Wu MG;Shen QS;Liu K;Yang CP;Chen YB
肺癌是全球癌症相关死亡的主要原因，非小细胞肺癌(NSCLC)约占所有病例的80%，是肺癌的主要亚类。G蛋白偶联受体激酶5(GRK5)已被证明在包括癌症在内的多种病理疾病的发生发展中起关键作用。免疫组织化学分析发现，GRK5在539例NSCLC癌组织中的表达明显高于99例正常非癌组织；女性和腺癌(ADC)NSCLC患者的GRK5阳性染色百分率明显高于男性和鳞癌(SCC)患者。此外，GRK5高表达的非小细胞肺癌患者的总体生存率低于低表达的患者。我们的研究结果表明，与正常人BEAS-2B细胞相比，非小细胞肺癌细胞系(GLC-82、SPC-A-1、H520、H838、H358、A549和H1299)中GRK5的mRNA和蛋白表达水平均升高，并在NSCLC癌组织中发现了许多GRK5突变。此外，我们发现GRK5的缺失抑制了NSCLC癌细胞的体外增殖、迁移和体内异种移植瘤的形成。此外，GRK5基因敲除促进细胞周期停滞于G2/M期，并诱导细胞凋亡。综上所述，我们的数据揭示了GRK5在NSCLC进展中的致癌作用，表明GRK5可能在未来被用作新的治疗靶点。
Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small-cell lung cancer (NSCLC) accounts for about 80% of all cases, which is the major subgroup of lung cancer. G protein-coupled receptor kinase 5 (GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological conditions including cancer. Here, we found that GRK5 expression was significantly increased in 539 NSCLC cancerous tissues than that in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also showed intensive higher positive staining percentage in female and adenocarcinoma (ADC) NSCLC patients than that in male and squamous cell carcinoma (SCC) patients, respectively. In addition, GRK5 high expression NSCLC patients had a worse overall survival rate than the low expression patients. We provided evidence showing that both the mRNA and protein expression levels of GRK5 were increased in NSCLC cancerous cell lines (GLC-82, SPC-A-1, H520, H838, H358, A549, and H1299) comparing with that in normal human bronchial epithelium cell line (BEAS-2B), and identified many GRK5 mutations in NSCLC cancerous tissues. In addition, we found that depletion of GRK5 inhibited NSCLC cancerous cell proliferation, migration in vitro, and xenograft tumor formation in vivo. Furthermore, GRK5 knockdown promoted cell cycle arrest at G2/M phase and induced cellular apoptosis. In summary, our data reveal an oncogenic role of GRK5 in NSCLC progression, indicating that GRK5 could be used as a new therapeutic target in future.
登录
查看更多内容
影响因子：
11
作者：
Tsai FM;Wu CC;Shyu RY;Wang CH;Jiang SY
通讯作者：
Jiang SY
影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1073/pnas.0804446105
发表时间：
2008-11-18
影响因子：
11.1
作者：
Sorriento, Daniela;Ciccarelli, Michele;Iaccarino, Guido
通讯作者：
Iaccarino, Guido
影响因子：
5.3
作者：
Johnson, LR;Scott, MGH;Pitcher, JA
通讯作者：
Pitcher, JA