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Hypoxia negatively regulates heparan sulfatase 2 expression in renal cancer cell lines
Author(s) -
Khurana Ashwani,
Tun Han W.,
Marlow Laura,
Copland John A.,
Dredge Keith,
Shridhar Viji
Publication year - 2012
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20824
Subject(s) - biology , gene knockdown , clear cell renal cell carcinoma , microbiology and biotechnology , vimentin , cancer research , heparan sulfate , cell growth , cell culture , cell , medicine , biochemistry , immunology , renal cell carcinoma , genetics , immunohistochemistry
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. © 2011 Wiley Periodicals, Inc.