Blocking TBK1 alleviated radiation-induced pulmonary fibrosis and epithelial-mesenchymal transition through Akt-Erk inactivation

Abstract

Lung cancer: Suppressing fibrosis during radiotherapy The risk of scarred tissues and respiratory distress during radiation treatment of lung cancer could be reduced by targeting an enzyme that alters healthy cells. Lung cancer radiotherapy often causes pulmonary fibrosis, excessive growth of fibrous tissues in the lungs, involving the transition of normal epithelial cells into an invasive form of multipotent stem cells. The development of pulmonary fibrosis limits the clinical application of radiotherapy. Hongjin Qu and co-workers at the Second Military University in Shanghai, China, previously demonstrated that the TANK-binding kinase 1 (TBK1) enzyme regulates this transition. Now, the team have shown that levels of TBK1 itself increased during radiation treatment, together with two proteins that would normally suppress alterations in healthy cells. Inhibiting TBK1, both in cell cultures and mouse models, reversed the cell transitions and prevented pulmonary fibrosis.