CHUN-HAN HOUChiang Y.-C.Fong Y.-C.Tang C.-H.2020-02-102020-02-1020110006-2952https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955608916&doi=10.1016%2fj.bcp.2011.03.016&partnerID=40&md5=595d9a539748bc92b8088c6fa4539bd4https://scholars.lib.ntu.edu.tw/handle/123456789/456369Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. WISP-1 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of matricellular proteins. However, the effect of WISP-1 on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that WISP-1 increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells (JJ012 cells). We also found that human chondrosarcoma tissues had significant expression of the WISP-1 which was higher than that in normal cartilage. α5β1 monoclonal antibody and MAPK kinase (MEK) inhibitors (PD98059 and U0126) inhibited the WISP-1-induced increase of the migration and MMP-2 up-regulation of chondrosarcoma cells. WISP-1 stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK and extracellular signal-regulated kinase (ERK). In addition, NF-κB inhibitors also suppressed the cell migration and MMP-2 expression enhanced by WISP-1. Moreover, WISP-1 increased NF-κB luciferase activity and binding of p65 to the NF-κB element on the MMP-2 promoter. Taken together, our results indicated that WISP-1 enhances the migration of chondrosarcoma cells by increasing MMP-2 expression through the α5β1 integrin receptor, FAK, MEK, ERK, p65 and NF-κB signal transduction pathway. ? 2011 Elsevier Inc. All rights reserved.[SDGs]SDG3CCN protein; focal adhesion kinase; gelatinase A; immunoglobulin enhancer binding protein; integrin receptor; luciferase; mitogen activated protein kinase; mitogen activated protein kinase kinase; synaptotagmin I; unclassified drug; very late activation antigen 5; WISP 1 protein; article; cancer cell culture; cell assay; cell migration; cell motility; chondrosarcoma; controlled study; enzyme activation; enzyme phosphorylation; human; human cell; metastasis potential; priority journal; promoter region; protein expression; protein function; protein protein interaction; signal transduction; upregulation; Base Sequence; Blotting, Western; Cell Line, Tumor; Cell Movement; Chondrosarcoma; Chromatin Immunoprecipitation; DNA Primers; Flow Cytometry; Humans; Integrin alpha5beta1; Intracellular Signaling Peptides and Proteins; Matrix Metalloproteinase 2; Polymerase Chain Reaction; Proto-Oncogene Proteinsjournal article10.1016/j.bcp.2011.03.016214536852-s2.0-79955608916