The tumor suppressor function of human sulfatase 1 (SULF1) in carcinogenesis.
BACKGROUND
Human sulfatase 1 (SULF1) was recently identified and shown to desulfate cellular heparan sulfate proteoglycans (HSPGs). Since sulfated HSPGs serve as co-receptors for many growth factors and cytokines, SULF1 was predicted to modulate growth factor and cytokine signaling.


CONCLUSIONS
The role of SULF1 in growth factor signaling and its effects on human tumorigenesis are under active investigation. Initial results show that SULF1 inhibits the co-receptor function of HSPGs in multiple receptor tyrosine kinase signaling pathways, particularly by the heparin binding growth factors--fibroblast growth factor 2, vascular endothelial growth factor, hepatocyte growth factor, PDGF, and heparin-binding epidermal growth factor (HB-EGF). SULF1 is downregulated in the majority of cancer cell lines examined, and forced expression of SULF1 decreases cell proliferation, migration, and invasion. SULF1 also promotes drug-induced apoptosis of cancer cells in vitro and inhibits tumorigenesis and angiogenesis in vivo.


CONCLUSIONS
Strategies targeting SULF1 or the interaction between SULF1 and the related sulfatase 2 will potentially be important in developing novel cancer therapies.
Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Jin-Ping
JP
Lai
Dalbir S
DS
Sandhu
Abdirashid M
AM
Shire
Lewis R
LR
Roberts
D017209:Apoptosis; D019175:DNA Methylation; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000502:physiology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D020935:MAP Kinase Signaling System; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D015238:Sulfotransferases / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D019812:Heparan Sulfate Proteoglycans; D056572:Histone Deacetylase Inhibitors; D017468:Receptors, Fibroblast Growth Factor; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; C470791:SULF1 protein, human; D015238:Sulfotransferases