LKB1 inhibits lung cancer progression through lysyl oxidase and extracellular matrix remodeling

On October 19th, the Proceedings of the National Academy of Sciences online published the latest findings of Prof. Hongbin Ji and Prof. Gaoxiang Ge from SIBCB. The scientists co-discovered that LKB1 inhibits lung cancer progression through lysyl oxidase and extracellular matrix remodeling. Their finding provides novel strategy to target lung cancer therapy.

 

LKB1 loss-of-function mutations, observed in ∼30% of human lung adenocarcinomas, contribute significantly to lung cancer malignancy progression. In the study, the researchers show that lysyl oxidase (LOX), negatively regulated by LKB1 through mTOR-HIF-1α signaling axis, mediate lung cancer progression. Moreover, inhibition of LOX activity dramatically alleviates lung cancer malignancy progression. Up-regulated LOX expression triggers excess collagen deposition in Lkb1-deficient lung tumors, and thereafter results in enhanced cancer cell proliferation and invasiveness through activation of β1 integrin signaling. High LOX level and activity correlate with poor prognosis and metastasis. Their findings provide evidence of how LKB1 loss of function promotes lung cancer malignancy through remodeling of extracellular matrix microenvironment, and identify LOX as a potential target for disease treatment in lung cancer patients.

 

This work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Chinese Academy of Sciences, and the Science and Technology Commission of Shanghai Municipality.