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

Chaoyu Ma, Yu Rong, Daniel R. Radiloff, Michael B. Datto, Barbara Centeno, Shideng Bao, Anthony Wai Ming Cheng, Fumin Lin, Shibo Jiang, Timothy J. Yeatman, Xiao Fan Wang

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

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 βig-h3/TGFBI (transforming growth factor, β-induced), an extracellular matrix protein secreted by colon cancer cells, is associated with high-grade human colon cancers. Ectopic expression of the βig-h3 protein enhanced the aggressiveness and altered the metastatic properties of colon cancer cells in vivo. Inhibition of βig-h3 expression dramatically reduced metastasis. Mechanistically, βig-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 αvβ5-Src signaling pathway. Thus, cancers associated with overexpression of βig-h3 may have an increased metastatic potential, leading to poor prognosis in cancer patients.

Original languageEnglish (US)
Pages (from-to)308-321
Number of pages14
JournalGenes and Development
Volume22
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

Keywords

  • Colon cancer
  • Extracellular matrix
  • Extravasation
  • Integrin αβ
  • Metastasis
  • βIg-h3/TGFBI

ASJC Scopus subject areas

  • General Medicine

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