Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells

Haiyun Deng, Ryouji Makizumi, T. S. Ravikumar, Huali Dong, Wancai Yang, Weng Lang Yang

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Bone morphogenetic protein (BMP), a member of the TGF-β superfamily, is involved in development, morphogenesis, cell proliferation and apoptosis. Dysregulation of BMP signaling has been suggested in tumorigenesis. In an analysis of human colon normal mucosa and tumors at different stages by immunohistochemistry, we observed that the intensity of BMP-4 staining in late-adenocarcinomas was stronger than that in normal mucosa and adenomas, while there was no difference in the staining of its receptors (BMPR-IA and BMPR-II) at all stages. The up-regulation of BMP-4 was further validated in another panel of tumor tissues by real-time RT-PCR, showing that BMP-4 mRNA levels in primary colonic carcinomas with liver metastasis were significantly higher than that in the matched normal mucosa. In order to understand the functional relevance of BMP-4 expression in colon cancer progression, BMP-4-overexpressing cell clones were generated from HCT116 cells. Overexpression of BMP-4 did not affect the HCT116 cell growth. The cells overexpressing BMP-4 became resistant to serum-starvation-induced apoptosis and exhibited enhanced migration and invasion characteristics. Overexpression of BMP-4 changed cell morphology to invasive spindle phenotype and induced the expression and activity of urokinase plasminogen activator (uPA). These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer.

Original languageEnglish (US)
Pages (from-to)1033-1044
Number of pages12
JournalExperimental Cell Research
Volume313
Issue number5
DOIs
StatePublished - Mar 10 2007
Externally publishedYes

Keywords

  • Apoptosis
  • BMP-4 expression
  • Colon cancer
  • Invasive phenotype
  • Urokinase plasminogen activator

ASJC Scopus subject areas

  • Cell Biology

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