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 language | English (US) |
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Pages (from-to) | 565-575 |
Number of pages | 11 |
Journal | Molecular Carcinogenesis |
Volume | 51 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2012 |
Keywords
- Cell migration
- Growth factor
- Heparan sulfatase 2
- VHL
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research