Regulation of chondrosarcoma invasion by MMP26

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• 作者：Xiaoshan Xu ; Jinxing Ma ; Chunxiao Li ; Wanqiu Zhao ; Yongqing Xu
• 关键词：Chondrosarcoma ; Cancer invasion ; MMP26 ; Wnt signaling
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：36
• 期：1
• 页码：365-369
• 全文大小：411 KB
• 参考文献：1. Wu MH, Lo JF, Kuo CH, Lin JA, Lin YM, Chen LM, et al. Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways. J Cell Physiol. 2012;227:3016-6. CrossRef
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  5. Zhang Y, Zhao H, Wang Y, Lin Y, Tan Y, Fang X, et al. Non-small cell lung cancer invasion and metastasis promoted by MMP-26. Mol Med Rep. 2011;4:1201-.
  6. Li D. Peaking of MMP-26 and TIMP-4 marks invasive transition in prostate cancer. Cell Res. 2006;16:741. CrossRef
  7. Yamamoto H, Vinitketkumnuen A, Adachi Y, Taniguchi H, Hirata T, Miyamoto N, et al. Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma. Carcinogenesis. 2004;25:2353-0. CrossRef
  8. Wang J, Su H, Han X, Xu K. Inhibition of fibroblast growth factor receptor signaling impairs metastasis of hepatocellular carcinoma. Tumour Biol. 2014. doi:10.1007/s13277-014-2384-0 .
  
• 作者单位：Xiaoshan Xu (1)
  Jinxing Ma (1)
  Chunxiao Li (1)
  Wanqiu Zhao (1)
  Yongqing Xu (1)
  
  1. Department of Orthopedic Surgery, Kunming General Hospital, 212 Daguan Road, Kunming, 650032, China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

The molecular mechanism underlying metastasis of chondrosarcoma (CS) remains unclarified. Here, we show that matrix metalloproteinase-26 (MMP26) level is significantly higher in the resected CS than in the adjacent healthy chondral tissue from the patients. To examine the role of MMP26 in CS invasion, we used a human CS line SW1353 and we either overexpressed or inhibited MMP26 in these cells. We found that overexpression of MMP26 in SW1353 cells increased cell invasiveness, while inhibition of MMP26 decreased cell invasiveness. To define the signal transduction cascades downstream of MMP26 activation, we applied specific inhibitors for PI3K, ERK/MAPK, JNK, and Wnt signaling, respectively, to the MMP26-overexpressing SW1353 cells. We found that only inhibition of Wnt signaling by either metformin or IWP-2 significantly decreased the effect of MMP26 on cancer cell invasion, possibly through increasing β-catenin phosphorylation. Further, a strong correlation was detected between MMP26 levels and the ratio of phosphorylated/total β-catenin in CS from the patients. Taken together, our study highlights MMP26-regulated Wnt signaling as a novel therapeutic target for CS.