S100A4 mediates endometrial cancer invasion and is a target of TGF-β1 signaling

Ran Xie, Matthew P. Schlumbrecht, Gregory L. Shipley, Susu Xie, Roland L. Bassett, Russell R. Broaddus

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The molecular mechanisms of endometrial cancer invasion are poorly understood. S100A4, also known as FSP1 (fibroblast-specific protein 1), has long been known to be a molecular marker of fibrosis in a variety of different fibrotic diseases of the lungs, liver, kidney, and heart. We demonstrate here that increased expression of S100A4 is associated with advanced stage endometrial cancer and decreased recurrence free survival. To verify the essential role of S100A4 in invasiveness of endometrial cancer, S100A4 expression was downregulated by RNAi in HEC-1A cells, which resulted in undetectable S100A4 protein and significantly decreased migration and invasion. Owing to the established connection between TGF-Β1 and S100A4 induction in experimental models of kidney and liver fibrosis, we next examined whether TGF-β1 could also regulate S100A4 in endometrial cancer cells. TGF-Β1 stimulated endometrial cancer cell migration and invasion with a concomitant increase in S100A4 protein. Induction of S100A4 was associated with the activation of Smads. TGF-Β1-mediated endometrial cancer cell motility was inhibited by S100A4 siRNA. In aggregate, these results suggest that S100A4 is a critical mediator of invasion in endometrial cancer and is upregulated by the TGF-Β1 signaling pathway. These results also suggest that endometrial cancer cell invasion and fibrosis share common molecular mechanisms.

Original languageEnglish (US)
Pages (from-to)937-947
Number of pages11
JournalLaboratory Investigation
Volume89
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

Keywords

  • Cancer invasion
  • Endometrial cancer
  • Epithelial-to-mesenchymal transition
  • S100A family genes
  • S100A4

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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