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Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.

Publication ,  Journal Article
Ma, C; Rong, Y; Radiloff, DR; Datto, MB; Centeno, B; Bao, S; Cheng, AWM; Lin, F; Jiang, S; Yeatman, TJ; Wang, X-F
Published in: Genes Dev
February 1, 2008

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.

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

February 1, 2008

Volume

22

Issue

3

Start / End Page

308 / 321

Location

United States

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

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Ma, C., Rong, Y., Radiloff, D. R., Datto, M. B., Centeno, B., Bao, S., … Wang, X.-F. (2008). Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev, 22(3), 308–321. https://doi.org/10.1101/gad.1632008
Ma, Chaoyu, Yu Rong, Daniel R. Radiloff, Michael B. Datto, Barbara Centeno, Shideng Bao, Anthony Wai Ming Cheng, et al. “Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.Genes Dev 22, no. 3 (February 1, 2008): 308–21. https://doi.org/10.1101/gad.1632008.
Ma C, Rong Y, Radiloff DR, Datto MB, Centeno B, Bao S, et al. Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev. 2008 Feb 1;22(3):308–21.
Ma, Chaoyu, et al. “Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation.Genes Dev, vol. 22, no. 3, Feb. 2008, pp. 308–21. Pubmed, doi:10.1101/gad.1632008.
Ma C, Rong Y, Radiloff DR, Datto MB, Centeno B, Bao S, Cheng AWM, Lin F, Jiang S, Yeatman TJ, Wang X-F. Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev. 2008 Feb 1;22(3):308–321.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

February 1, 2008

Volume

22

Issue

3

Start / End Page

308 / 321

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Receptors, Vitronectin
  • Oligopeptides
  • Neovascularization, Pathologic
  • Neoplasm Invasiveness
  • Molecular Sequence Data
  • Mice, SCID
  • Mice
  • Lung Neoplasms
  • Intercellular Junctions