| Fibulin-3 is a novel TGF-beta pathway inhibitor in the breast cancer microenvironment |
| Tian,H.; Liu,J.; Chen,J.; Gatza,M. L.; Blobe,G. C.
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| 2015-11-05
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| 发表期刊 | ONCOGENE
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| 卷号 | 34期号:45页码:5635-5647 |
| 摘要 | Transforming growth factor-beta (TGF-beta) is an important regulator of breast cancer progression. However, how the breast cancer microenvironment regulates TGF-beta signaling during breast cancer progression remains largely unknown. Here, we identified fibulin-3 as a secreted protein in the breast cancer microenvironment, which efficiently inhibits TGF-beta signaling in both breast cancer cells and endothelial cells. Mechanistically, fibulin-3 interacts with the type I TGF-beta receptor (T beta RI) to block TGF-beta induced complex formation of T beta RI with the type II TGF-beta receptor (T beta RII) and subsequent downstream TGF-beta signaling. Fibulin-3 expression decreases during breast cancer progression, with low fibulin-3 levels correlating with a poorer prognosis. Functionally, high fibulin-3 levels inhibited TGF-beta-induced epithelial-mesenchymal transition (EMT), migration, invasion and endothelial permeability, while loss of fibulin-3 expression/function promoted these TGF-beta-mediated effects. Further, restoring fibulin-3 expression in breast cancer cells inhibited TGF-beta signaling, breast cancer cell EMT, invasion and metastasis in vivo. These studies provide a novel mechanism for how TGF-beta signaling is regulated by the tumor microenvironment, and provide insight into targeting the TGF-beta signaling pathway in human breast cancer patients. |
| DOI | 10.1038/onc.2015.13
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| 收录类别 | SCI
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| 语种 | 英语
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| WOS记录号 | WOS:000364594300005
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| 引用统计 |
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kib.ac.cn/handle/151853/25239
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| 专题 | 植物化学与西部植物资源持续利用国家重点实验室
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推荐引用方式
GB/T 7714 |
Tian,H.,Liu,J.,Chen,J.,et al. Fibulin-3 is a novel TGF-beta pathway inhibitor in the breast cancer microenvironment[J]. ONCOGENE,2015,34(45):5635-5647.
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| APA |
Tian,H.,Liu,J.,Chen,J.,Gatza,M. L.,&Blobe,G. C..(2015).Fibulin-3 is a novel TGF-beta pathway inhibitor in the breast cancer microenvironment.ONCOGENE,34(45),5635-5647.
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| MLA |
Tian,H.,et al."Fibulin-3 is a novel TGF-beta pathway inhibitor in the breast cancer microenvironment".ONCOGENE 34.45(2015):5635-5647.
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