期刊
CARCINOGENESIS
卷 35, 期 8, 页码 1707-1716出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgu023
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资金
- Ministry of Science and Technology of China [2009CB918903]
- National Institutes of Health [CA172136, CA106348, CA129829]
- Tianjin Municipal Education Commission Foundation [2012ZD01]
- American Cancer Society [RSG-10-124-01-CCE]
The 5 year survival rate of lung cancer is <20%, with most patients dying from distant metastasis. However, the molecular mechanisms underlying lung cancer invasion and metastasis have not been fully characterized. In this study, we found that fibulin-3, a fibulin family extracellular matrix protein, functions as a suppressor of lung cancer invasion and metastasis. Fibulin-3 was downregulated in large fractions of lung tumors and cell lines, and inhibited lung cancer cell invasion and the expression of matrix metalloproteinase-7 (MMP-7), a promoter of lung cancer invasion. The expression levels of fibulin-3 and MMP-7 were inversely correlated in lung tumors. Fibulin-3 inhibited extracellular signal-regulated kinase (ERK) to activate glycogen synthase kinase 3 beta and suppress Wnt/beta-catenin signaling, which induces MMP-7 expression in lung cancer cells. Furthermore, fibulin-3 expression impeded the growth and metastasis of lung tumors in mice. Collectively, these results suggest that downregulation of fibulin-3 contributes to lung cancer invasion and metastasis by activating Wnt/beta-catenin signaling and MMP-7 expression.
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