Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.
Metastasis, the major cause of cancer death, is a multistep process that requires interactions between cancer cells and stromal cells and between cancer cells and extracellular matrix. Molecular alterations of the extracellular matrix in the tumor microenvironment have a considerable impact on the metastatic process during tumorigenesis. Here we report that elevated expression of betaig-h3/TGFBI (transforming growth factor, beta-induced), an extracellular matrix protein secreted by colon cancer cells, is associated with high-grade human colon cancers. Ectopic expression of the betaig-h3 protein enhanced the aggressiveness and altered the metastatic properties of colon cancer cells in vivo. Inhibition of betaig-h3 expression dramatically reduced metastasis. Mechanistically, betaig-h3 appears to promote extravasation, a critical step in the metastatic dissemination of cancer cells, by inducing the dissociation of VE-cadherin junctions between endothelial cells via activation of the integrin alphavbeta5-Src signaling pathway. Thus, cancers associated with overexpression of betaig-h3 may have an increased metastatic potential, leading to poor prognosis in cancer patients.
Duke Scholars
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Related Subject Headings
- Transforming Growth Factor beta
- Receptors, Vitronectin
- Oligopeptides
- Neovascularization, Pathologic
- Neoplasm Invasiveness
- Molecular Sequence Data
- Mice, SCID
- Mice
- Lung Neoplasms
- Intercellular Junctions
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transforming Growth Factor beta
- Receptors, Vitronectin
- Oligopeptides
- Neovascularization, Pathologic
- Neoplasm Invasiveness
- Molecular Sequence Data
- Mice, SCID
- Mice
- Lung Neoplasms
- Intercellular Junctions