title: Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells.
abstract: Tight junction proteins (TJPs) including Claudins, Occludin and tight junction associated protein Zonula occludens-1 (ZO-1), are the most apical component of junctional complex that mediates cell-cell adhesion in epithelial and endothelial cells. In human malignancies, TJPs are often deregulated and affect cellular behaviors of tumor cells. In this study, we investigated alternations of TJPs and related biological characteristics in human osteosarcoma (OS). Claudin1 was increased in the metastatic OS cells (KRIB and KHOS) compared with the normal osteoblast cells (hFOB1.19) or primary tumor cells (HOS and U2OS), whereas no significant difference was found in Occludin and ZO-1. Immunohistochemistry, immunofluorescence and Western blotting revealed that Claudin1 was initially localized at cell junctions of normal osteoblasts, but substantially delocalized to the nucleus of metastatic OS cells. Phenotypically, inhibition of the nucleus Claudin1 expression compromised the metastatic potential of KRIB and KHOS cells. Moreover, we found that protein kinase C (PKC) but not PKA phosphorylation influenced Claudin1 expression and cellular functions, as PKC inhibitor (Go 6983 and Staurosporine) or genetic silencing of PKC reduced Claudin1 expression and decreased the motility of KRIB and KHOS cells. Taken together, our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells.
authors.affiliation: Department of Orthopaedics, The Affiliated People's Hospital of Guiyang Medical University, Guiyang, Guizhou Province 550002, PR China.
authors.forename: Yuekui
authors.initials: Y
authors.lastname: Jian
authors.affiliation: Department of Orthopaedics, The Affiliated People's Hospital of Guiyang Medical University, Guiyang, Guizhou Province 550002, PR China.
authors.forename: Changqiong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The Affiliated People's Hospital of Guiyang Medical University, Guiyang, Guizhou Province 550002, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Affiliated People's Hospital of Guiyang Medical University, Guiyang, Guizhou Province 550002, PR China. Electronic address: drtxb_guiyang@sina.com.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Tian
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D062445:Claudin-1 / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C
keywords: Claudin1; Metastasis; Osteosarcoma; Protein kinase C