Hypoxia negatively regulates heparan sulfatase 2 expression in renal cancer cell lines

Ashwani Khurana, Han W. Tun, Laura Marlow, John A. Copland, Keith Dredge, Viji Shridhar

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Inactivation of von Hippel-Lindau (VHL), a tumor suppressor gene is often associated with clear cell renal cell carcinoma (ccRCC). VHL inactivation leads to multitude of responses including enhanced growth factor signaling such as bFGF2, SDF-1α, and HGF. Here, we have identified a novel VHL-inducible gene, heparan sulfatase 2 (HSulf-2) that attenuates heparan-binding growth factor such as bFGF2 signaling. VHL-mediated HIF-1 alpha degradation was essential to restore HSulf-2 expression. Mechanistically, HSulf-2 negatively regulated vimentin expression and knockdown of vimentin abolished cell migration. This study reveals a novel layer of regulation of heparan-binding growth factor signaling via modulation of heparan sulfate by HSulf-2 in ccRCC.

Original languageEnglish (US)
Pages (from-to)565-575
Number of pages11
JournalMolecular Carcinogenesis
Volume51
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • Cell migration
  • Growth factor
  • Heparan sulfatase 2
  • VHL

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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