title: Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation.
abstract: Wnt/β-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 β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-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.
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Chu
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China. Electronic address: baohuihan1@163.com.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C493709:RUNX2 protein, human; D051176:beta Catenin
keywords: ALP; APC; Bone metastasis; DKK1; Dickkopf1; Dishevelled; Dvl; ECM; GSK-3β; NSCLC; Non-small-cell lung cancer; Osteoblast differentiation; Wnt signaling; adenomatous polyposis coli; alkaline phosphatase; extracellular matrix; glycogen synthase kinase 3β; non-small-cell lung cancer