GRK5 functions as an oncogenic factor in non-small-cell lung cancer.

Autor: Jiang LP; 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.; Kunming College of Life Science, University of Chinese Academy of Sciences, 100049, Beijing, China., Fan SQ; Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Xiong QX; Kunming Medical University, 650223, Kunming, China., Zhou YC; Kunming Medical University, 650223, Kunming, China., Yang ZZ; Kunming Medical University, 650223, Kunming, China., Li GF; Kunming Medical University, 650223, Kunming, China., Huang YC; Kunming Medical University, 650223, Kunming, China., Wu MG; Kunming Medical University, 650223, Kunming, China., Shen QS; 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.; Kunming College of Life Science, University of Chinese Academy of Sciences, 100049, Beijing, China., Liu K; 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.; Kunming College of Life Science, University of Chinese Academy of Sciences, 100049, Beijing, China., Yang CP; 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. cuipingyang@mail.kiz.ac.cn., Chen YB; 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. ybchen@mail.kiz.ac.cn.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2018 Feb 20; Vol. 9 (3), pp. 295. Date of Electronic Publication: 2018 Feb 20.
DOI: 10.1038/s41419-018-0299-1
Abstrakt: 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.
Databáze: MEDLINE