Osteoblast-derived WISP-1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126

Huai Ching Tai, An Chen Chang, Hong Jeng Yu, Chao Yuan Huang, Yu Chieh Tsai, Yu Wei Lai, Hui Lung Sun, Chih Hsin Tang, Shih Wei Wang

研究成果: 雜誌貢獻文章同行評審

55 引文 斯高帕斯(Scopus)

摘要

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 avß1 integrin, FAK, and p38 signaling pathways. Thus, WISP-1 may be a new molecular therapeutic target in PCa bone metastasis.
原文英語
頁(從 - 到)7589-7598
頁數10
期刊Oncotarget
5
發行號17
DOIs
出版狀態已發佈 - 2014
對外發佈

ASJC Scopus subject areas

  • 腫瘤科

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