title: The Biological Effects of Dickkopf1 on Small Cell Lung Cancer Cells and Bone Metastasis.
abstract: The bone is among the most common sites of metastasis in patients with lung cancer. Over 30%-40% of lung cancers can develop bone metastasis, and no effective therapeutic methods exist in clinic cases. Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferentially metastasizes to the skeleton. However, the role of DKK1 in osteotropism of small cell lung cancer (SCLC) remains to be elucidated. This study aimed to define the role of DKK1 in SCLC bone metastasis and investigate the underlying mechanisms. Our results demonstrated that the expression level of DKK1 was dramatically higher in bone metastatic SCLC cells (SBC-5 cell line) compared with that in cells without bone metastatic ability (SBC-3 cell line). Therefore, we hypothesized that DKK1 was involved in the bone metastasis of SCLC. We then suppressed the DKK1 expression in SBC-5 cells by RNAi and found that downregulation of DKK1 can inhibit cell proliferation, colony formation, cell migration, and invasion, but increase the apoptosis rate. Downregulation of DKK1 did not affect the cell cycle progression of SBC-5 cells in vitro. In vivo, downregulated DKK1 in SBC-5 cells resulted in attenuated bone metastasis. These results indicated that DKK1 may be an important regulator in bone metastases of SCLC, and targeting DKK1 may be an effective method to prevent and treat skeleton metastases in SCLC cases.
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Pang
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Ningqiang
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Mi
authors.initials: M
authors.lastname: Jiao
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xin
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Tongfei
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiP.R. China.
authors.forename: Helong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D055752:Small Cell Lung Carcinoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins