Osteoblast-derived WISP-1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126
Journal
Oncotarget
Journal Volume
5
Journal Issue
17
Pages
7589-7598
Date Issued
2014
Author(s)
Chang A.-C.
Lai Y.-W.
Sun H.-L.
Tang C.-H.
Wang S.-W.
Abstract
Bone metastases of prostate cancer (PCa) may cause intractable pain. Wnt-induced secreted protein-1 (WISP-1) belongs to the CCN family (CTGF/CYR61/NOV) that plays a key role in bone formation. We found that osteoblast-conditioned medium (OBCM) stimulates migration and vascular cell adhesion molecule-1 (VCAM-1) expression in human PCa (PC3 and DU145) cells. Osteoblast transfection with WISP-1 shRNA reduced OBCM-mediated PCa migration and VCAM-1 expression. Stimulation of PCa with OBCM or WISP-1 elevated focal adhesion kinase (FAK) and p38 phosphorylation. Either FAK and p38 inhibitors or siRNA abolished osteoblast-derived WISP-1-induced migration and VCAM-1 expression. Osteoblast-derived WISP-1 inhibited miR-126 expression. Moreover, miR-216 mimic reversed the WISP-1-enhanced migration and VCAM-1 expression. This study suggests that osteoblast-derived WISP-1 promotes migration and VCAM-1 expression in human PCa cells by down-regulating miR-126 expression via av?1 integrin, FAK, and p38 signaling pathways. Thus, WISP-1 may be a new molecular therapeutic target in PCa bone metastasis.
SDGs
Other Subjects
alphaVbeta5 integrin; CCN protein; focal adhesion kinase; microRNA 126; mitogen activated protein kinase; short hairpin RNA; synaptophysin; unclassified drug; vascular cell adhesion molecule 1; Wnt induced secreted protein 1; CCN protein; microRNA; MIRN126 microRNA, human; oncoprotein; small interfering RNA; vascular cell adhesion molecule 1; WISP1 protein, human; Article; bone metastasis; cell migration; cell motility; controlled study; culture medium; down regulation; DU145 cell line; enzyme activity; gene expression; genetic transfection; human; human cell; osteoblast conditioned medium; prostate cancer; prostate cancer cell line; protein expression; protein phosphorylation; signal transduction; upregulation; biosynthesis; cell line; down regulation; genetics; male; metabolism; osteoblast; pathology; prostate tumor; real time polymerase chain reaction; tumor cell line; tumor invasion; Western blotting; Blotting, Western; CCN Intercellular Signaling Proteins; Cell Line; Cell Line, Tumor; Down-Regulation; Humans; Male; MicroRNAs; Neoplasm Invasiveness; Osteoblasts; Prostatic Neoplasms; Proto-Oncogene Proteins; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; Transfection; Vascular Cell Adhesion Molecule-1
Publisher
Impact Journals LLC
Type
journal article