Overexpression of bone morphogenetic protein 4 enhances the invasiveness of Smad4-deficient human colorectal cancer cells

Haiyun Deng, T. S. Ravikumar, Weng Lang Yang

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Bone morphogenetic proteins (BMP), a member of the TGF-β superfamily, have broad activities in regulating various kinds of cellular behaviors. Previously, we have demonstrated that BMP-4 is up-regulated in human colonic adenocarcinoma and promotes the invasive phenotypes of human colorectal cancer HCT116 cells. Smad4 is a central mediator in BMP signaling pathway and it is frequently mutated in metastatic colorectal cancers. To address whether Smad4 was required for enhancing metastatic potentials by BMP-4 in colorectal cancer, we generated BMP-4 overexpressing clones from Smad4-deficient SW480 cells. The growth rate of BMP-4 overexpressing cells was slightly higher than that of empty-vector controls. Overexpression of BMP-4 resulted in an increased expression of vimentin, a marker of epithelial-mesenchymal transition, and caused the changes of cell morphology, spreading and formation of focal adhesions. BMP-4 overexpressing cells increased cell adhesion on fibronectin and collagen, and augmented cell migration and invasion potentials in comparison to empty-vector controls. The induction of cell migration by BMP-4 overexpression was inhibited by BMP-4 siRNA. To further identify the target genes of the elevated BMP-4 signaling in SW480 cells, an oligonucleotide microarray was performed. Among 46,000 genes, 91 genes (65 up-regulated and 26 down-regulated) with 2-fold difference have been identified between BMP-4 overexpressing and empty-vector cells. This study demonstrates that Smad4 is dispensable for enhanced invasiveness of human colorectal cancer cells due to BMP-4 overexpression.

Original languageEnglish (US)
Pages (from-to)220-231
Number of pages12
JournalCancer Letters
Volume281
Issue number2
DOIs
StatePublished - Aug 28 2009
Externally publishedYes

Keywords

  • BMP-4
  • Colorectal cancer
  • Gene expression
  • Invasive phenotype
  • Smad4

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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