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

被引：9

作者：

Khurana, Ashwani

Tun, Han W. ^{[2
]}

Marlow, Laura ^{[3
]}

Copland, John A. ^{[3
]}

Dredge, Keith ^{[4
]}

Shridhar, Viji ^{[1
]}

机构：

[1] Mayo Clin, Ctr Canc, Dept Expt Pathol, Coll Med, Rochester, MN 55905 USA

[2] Mayo Clin, Div Hematol Oncol, Jacskonville, FL USA

[3] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA

[4] Progen Pharmaceut Ltd, Brisbane, Qld, Australia

来源：

MOLECULAR CARCINOGENESIS | 2012年 / 51卷 / 07期

基金：

美国国家卫生研究院;

关键词：

heparan sulfatase 2; growth factor; cell migration; VHL; TUMOR-SUPPRESSOR GENE; BREAST-CANCER; HSULF-1; EXPRESSION; IN-VIVO; GROWTH; CARCINOMA; PROTEIN; PROTEOGLYCANS; REPRESSION; ALPHA;

D O I：

10.1002/mc.20824

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-1a, 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. (c) 2011 Wiley Periodicals, Inc.

引用

页码：565 / 575

页数：11

共 40 条

[31] Hypoxia down-regulates CCAAT/Enhancer binding protein-α expression in breast cancer cells [J].