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

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

Research output: Contribution to journalReview article

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalJournal of gastrointestinal cancer
Volume39
Issue number1-4
DOIs
StatePublished - Mar 2008

Keywords

  • Methylation
  • SULF1
  • Sulfatase
  • Tumor suppressor

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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