Lung cancer is featured with high mortality,with a 15%five-year survival rate worldwide.Genetic alterations,such as loss of function of tumor suppressor genes,frequently contribute to lung cancer initiation,progression and metastasis.Liver kinase B1(LKB1),as a serine/threonine kinase and tumor suppressor,is frequently mutated and inactivated in non-small cell lung cancer(NSCLC).Recent studies have provided strong evidences that LKB1 loss promotes lung cancerigenesis process,especially lung cancer progression and metastasis.This review will summarize recent progress on how LKB1 modulates the process of lung cancerigenesis,emphasizing on LKB1 downstream signaling pathways and biological functions.We will further discuss the potential development of prognostic biomarkers or therapeutic targets in lung cancer clinic based on the molecular alteration associated with deregulated LKB1 signaling.
Enzymes involved in collagen biosynthesis, including lysyl oxidase （LOX）, have been proposed as potential therapeutic targets for idio- pathic pulmonary fibrosis. LOX expression is significantly upregulated in bleomycin （BLM）-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory ceU infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expres- sion of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subse- quent fibrosis process after lung injury.
Tao ChengQingbo LiuRui ZhangYing ZhangJianfeng ChenRonghuan YuGaoxiang Ge
