Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway

• Main Authors: Jian Zhou, Guimei Qu, Ge Zhang, Zuoren Wu, Jing Liu, Dawei Yang, Jing Li, Meijia Chang, Hengshan Zeng, Jie Hu, Tao Fang, Yuanlin Song, Chunxue Bai
• Format: Article
• Language: English
• Published: BMC 2019-02-01
• Series: Journal of Experimental & Clinical Cancer Research
• Subjects: Non-small cell lung cancer; Glycerol kinase 5; Gefitinib; Stearoyl-CoA desaturase-1
• Online Access: http://link.springer.com/article/10.1186/s13046-019-1057-7

Abstract Background Drug resistance is common in cancer chemotherapy. This study investigates the role of Glycerol kinase 5 (GK5) in mediating gefitinib resistance in NSCLC. Methods The exosomal mRNA of GK5 was detected using a tethered cationic lipoplex nanoparticle (TCLN) biochip. Real-time PCR and Western blot were used to examine the expression of GK5 mRNA and protein in gefitinib-sensitive and -resistant human lung adenocarcinoma cells. The cell counting kit-8, EdU assay, flow cytometry, and JC-1 dye were used to measure cell proliferation, cell cycle, and the mitochondrial membrane potential. Results We found that the exosomal mRNA of GK5 in the plasma of patients with gefitinib-resistant adenocarcinoma was significantly higher compared with that of gefitinib-sensitive patients. The mRNA and protein levels of GK5 were significantly upregulated in gefitinib-resistant human lung adenocarcinoma PC9R and H1975 cells compared with gefitinib-sensitive PC9 cells. Silencing GK5 in PC9R cells induced mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via SREBP1/SCD1 signaling pathway. Conclusions We demonstrated that GK5 confers gefitinib resistance in lung cancer by inhibiting apoptosis and cell cycle arrest. GK5 could be a novel therapeutic target for treatment of NSCLC with resistance to EGFR tyrosine kinase inhibitors.