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J Gastrointest Cancer. 2008;39(1-4):149-58. doi: 10.1007/s12029-009-9058-y. Epub 2009 Apr 17.

The tumor suppressor function of human sulfatase 1 (SULF1) in carcinogenesis.

Author information

  • 1Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

INTRODUCTION:

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.

DISCUSSION:

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.

CONCLUSION:

Strategies targeting SULF1 or the interaction between SULF1 and the related sulfatase 2 will potentially be important in developing novel cancer therapies.

PMID:
19373441
[PubMed - indexed for MEDLINE]
PMCID:
PMC2925118
Free PMC Article

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