CCN6-mediated MMP-9 activation enhances metastatic potential of human chondrosarcoma

Huey En Tzeng, Chih Hsin Tang, Sz Hua Wu, Hsien Te Chen, Yi Chin Fong, Yung Chang Lu, Wei Cheng Chen, Hsien Da Huang, Chih Yang Lin, Shih Wei Wang

研究成果: 雜誌貢獻文章同行評審

21 引文 斯高帕斯(Scopus)


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 NF-κB inhibitors or short interfering (si)RNAs. Our investigations indicate that CCN6 facilitates metastasis through the PI3K/Akt/mTOR/NF-κB 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.
期刊Cell Death and Disease
出版狀態已發佈 - 10月 1 2018

ASJC Scopus subject areas

  • 免疫學
  • 細胞與分子神經科學
  • 細胞生物學
  • 癌症研究


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