Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

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• 作者：Tianqing Chu ; Jiajun Teng ; Liyan Jiang ; Hua Zhong ; Baohui Han
• 关键词：NSCLC ; non-small-cell lung cancer ; ECM ; extracellular matrix ; ALP ; alkaline phosphatase ; DKK1 ; Dickkopf1 ; Dvl ; Dishevelled ; GSK-3尾 ; glycogen synthase kinase 3尾 ; APC ; adenomatous polyposis coli
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：17 January, 2014
• 年：2014
• 卷：443
• 期：3
• 页码：962-968
• 全文大小：1176 K

文摘

Wnt/尾-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of 尾-catenin and RUNX2, as well as inhibiting the nuclear translocation of 尾-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.