Fibulin-3 suppresses Wnt/β-catenin signaling and lung cancer invasion.

Abstract

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 3β and suppress Wnt/β-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/β-catenin signaling and MMP-7 expression.

• Authors: Xiaojun Chen, Jie Meng, Wen Yue, Jian Yu, Jie Yang, Zhi Yao, Lin Zhang
• Journal: Carcinogenesis (Carcinogenesis) Vol. 35 Issue 8 Pg. 1707-16 (Aug 2014) ISSN: 1460-2180 [Electronic] England
• PMID: 24480807 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• EFEMP1 protein, human
• Extracellular Matrix Proteins
• RNA, Messenger
• Wnt Proteins
• beta Catenin
• MMP7 protein, human
• Matrix Metalloproteinase 7

Topics

• Animals
• Apoptosis
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (metabolism, prevention & control, secondary)
• Cell Movement
• Cell Proliferation
• DNA Methylation
• Extracellular Matrix Proteins (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung (metabolism, pathology)
• Lung Neoplasms (metabolism, pathology, prevention & control)
• Matrix Metalloproteinase 7 (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Promoter Regions, Genetic
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Tumor Cells, Cultured
• Wnt Proteins (genetics, metabolism)
• Xenograft Model Antitumor Assays
• beta Catenin (genetics, metabolism)