title: Hypoxia negatively regulates heparan sulfatase 2 expression in renal cancer cell lines.
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.
authors: Department of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors: Ashwani
authors: A
authors: Khurana
authors: Han W
authors: HW
authors: Tun
authors: Laura
authors: L
authors: Marlow
authors: John A
authors: JA
authors: Copland
authors: Keith
authors: K
authors: Dredge
authors: Viji
authors: V
authors: Shridhar
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D013429:Sulfatases / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; D013429:Sulfatases; C021346:heparan sulfate sulfatase