RUVBL1, a novel C-RAF-binding protein, activates the RAF/MEK/ERK pathway to promote lung cancer tumorigenesis

• Published in: Biochemical and biophysical research communications 2018-04, Vol.498 (4), p.932-939
• Main Authors: Guo, Hui, Zhang, Xin-Yu, Peng, Jun, Huang, Ying, Yang, Yang, Liu, Ying, Guo, Xiao-Xi, Hao, Qian, An, Su, Xu, Tian-Rui
• Format: Article
• Language: English
• Subjects: A549 Cells; ATPases Associated with Diverse Cellular Activities - pharmacology; ATPases Associated with Diverse Cellular Activities - physiology; C-RAF kinase; Carcinogenesis - drug effects; Carcinogenesis - metabolism; Carrier Proteins - pharmacology; Carrier Proteins - physiology; Cell Movement - drug effects; Cell Proliferation - drug effects; DNA Helicases - pharmacology; DNA Helicases - physiology; Humans; Lung cancer; Lung Neoplasms - etiology; MAP Kinase Signaling System; Phosphorylation - drug effects; Proto-Oncogene Proteins c-raf - metabolism; RUVBL1; Signal Transduction - drug effects; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.03.084

Lung cancer remains the leading cause of cancer-related deaths in the world. The RAF/MEK/ERK pathway controls many fundamental cellular functions and plays key roles in lung carcinogenesis. However, the proteins that regulate this pathway remain largely unknown. Here, we identified a novel C-RAF-binding protein, RUVBL1, which activates the RAF/MEK/ERK pathway by inhibiting phosphorylation of the C-RAF protein at serine 259. RUVBL1 expression was elevated in lung adenocarcinoma tissues. In addition, knocking out RUVBL1 effectively inhibited the proliferation and invasion of A549 cells. In vivo experiments, RUVBL1 deficiency significantly decreased the tumorigensis of lung cancer. In conclusion, we have shown that RUVBL1 could activate the RAF/MEK/ERK pathway by inhibiting phosphorylation of the C-RAF protein at serine 259, to promote lung cancer progression. Therefore, RUVBL1 could represent a novel therapeutic target for lung cancer treatment.