標題: CCN6-mediated MMP-9 activation enhances metastatic potential of human chondrosarcoma
作者: Tzeng, Huey-En
Tang, Chih-Hsin
Wu, Sz-Hua
Chen, Hsien-Te
Fong, Yi-Chin
LU, Yung-Chang
Chen, Wei-Cheng
Huang, Hsien-Da
Lin, Chih-Yang
Wang, Shih-Wei
交大名義發表
生物科技學系
生物資訊及系統生物研究所
National Chiao Tung University
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
公開日期: 20-Sep-2018
摘要: Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. WNT1-inducible signaling pathway protein-3 (WISP-3, also termed CCN6) belongs to the CCN family of proteins and is implicated in the regulation of various cellular functions, such as cell proliferation, differentiation, and migration. It is unknown as to whether CCN6 affects human chondrosarcoma metastasis. We show how CCN6 promotes chondrosarcoma cell migration and invasion via matrix metallopeptidase-9 (MMP)-9 expression. These effects were abolished by pretreatment of chondrosarcoma cells with PI3K, Akt, mTOR, and NE-KB inhibitors or short interfering (si)RNAs. Our investigations indicate that CCN6 facilitates metastasis through the PI3K/Akt/mTOR/NE-KB signaling pathway. CCN6 and MMP-9 expression was markedly increased in the highly migratory JJ012(S10) cell line compared with the primordial cell line (JJ012) in both in vitro and in vivo experiments. CCN6 knockdown suppressed MMP-9 production in JJ012(S10) cells and attenuated cell migration and invasion ability. Importantly, CCN6 knockdown profoundly inhibited chondrosarcoma cell metastasis to lung. Our findings reveal an important mechanism underlying CCN6-induced metastasis and they highlight the clinical significance between CCN6 and MMP-9 in regard to human chondrosarcoma. CCN6 appears to be a promising therapeutic target in chondrosarcoma metastasis.
URI: http://dx.doi.org/10.1038/s41419-018-1008-9
http://hdl.handle.net/11536/148245
ISSN: 2041-4889
DOI: 10.1038/s41419-018-1008-9
期刊: CELL DEATH & DISEASE
Volume: 9
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