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

Biochem Biophys Res Commun. 2018 Apr 15;498(4):932-939. doi: 10.1016/j.bbrc.2018.03.084. Epub 2018 Mar 15.

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.

Keywords: A549 cells; C-RAF kinase; Lung cancer; RUVBL1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • ATPases Associated with Diverse Cellular Activities / pharmacology
  • ATPases Associated with Diverse Cellular Activities / physiology*
  • 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 Neoplasms / etiology*
  • MAP Kinase Signaling System*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Signal Transduction / drug effects*
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Proto-Oncogene Proteins c-raf
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human