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The Tumor Suppressor Function of Human Sulfatase 1 (SULF1) in Carcinogenesis

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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.

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Acknowledgments

This study was supported by the Mayo Clinic and Mayo Clinic Cancer Center, NIH Grants CA82862 and CA100882, an Industry Research Scholar Award from the Foundation for Digestive Health and Nutrition, a Harold Amos Medical Faculty Development Award from The Robert Wood Johnson Foundation, a generous gift from The Richard M. Schulze Family Foundation, and the Miles and Shirley Fiterman Center for Digestive Diseases at the Mayo Clinic, Rochester, MN, USA. Dr. Roberts and Mayo Clinic have a potential financial interest associated with technology used in research referenced in this review. The authors thank Vicki Campion for secretarial assistance.

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Authors and Affiliations

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

    Jin-Ping Lai, Dalbir S. Sandhu, Abdirashid M. Shire & Lewis R. Roberts

  2. Miles and Shirley Fiterman Center for Digestive Diseases, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Lewis R. Roberts

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  1. Jin-Ping Lai
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Correspondence to Lewis R. Roberts.

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Lai, JP., Sandhu, D.S., Shire, A.M. et al. The Tumor Suppressor Function of Human Sulfatase 1 (SULF1) in Carcinogenesis. J Gastrointest Canc 39, 149–158 (2008). https://doi.org/10.1007/s12029-009-9058-y

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  • DOI: https://doi.org/10.1007/s12029-009-9058-y

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