机构:[1]Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Jiao Chang Dong Lu 32, 650223 Kunming, China.[2]Kunming College of Life Science, University of Chinese Academy of Sciences, 100049 Beijing, China[3]Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.[4]Kunming Medical University, 650223 Kunming, China
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.
基金:
This study was equally supported by the National Key Research and
Development Program of China (2016YFA0100900) and Strategic Priority
Research Program of the Chinese Academy of Sciences (XDB13000000). Also
was supported by National Nature Science Foundation of China (U1502224,
81672764, 81772996), Yunnan province High-Level Talents Introduced
program 2013HA021 and Yunnan Applied Basic Research Projects (2014FA038,
2016FA009, 2014FB182). C.-P.Y. was also supported by the Chinese Academy of
Sciences Western Light Program, Youth Innovation Promotion Association,
CAS.
第一作者机构:[1]Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Jiao Chang Dong Lu 32, 650223 Kunming, China.[2]Kunming College of Life Science, University of Chinese Academy of Sciences, 100049 Beijing, China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Li-Ping Jiang,Song-Qing Fan,Qiu-Xia Xiong,et al.GRK5 functions as an oncogenic factor in non-small-cell lung cancer[J].CELL DEATH & DISEASE.2018,(9):doi:10.1038/s41419-018-0299-1.
APA:
Li-Ping Jiang,Song-Qing Fan,Qiu-Xia Xiong,Yong-Chun Zhou,Zuo-Zhang Yang...&Yong-Bin Chen.(2018).GRK5 functions as an oncogenic factor in non-small-cell lung cancer.CELL DEATH & DISEASE,,(9)
MLA:
Li-Ping Jiang,et al."GRK5 functions as an oncogenic factor in non-small-cell lung cancer".CELL DEATH & DISEASE ..9(2018)