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

RUVBL1 是一种新型 C-RAF 结合蛋白,可激活 RAF/MEK/ERK 通路促进肺癌肿瘤发生

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作者:Hui Guo, Xin-Yu Zhang, Jun Peng, Ying Huang, Yang Yang, Ying Liu, Xiao-Xi Guo, Qian Hao, Su An, Tian-Rui Xu

Abstract

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.

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