Heparin-degrading sulfatases in hepatocellular carcinoma: Roles in pathogenesis and therapy targets

Jin Ping Lai, James R. Thompson, Dalbir S. Sandhu, Lewis R. Roberts

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage at which there are limited treatment options. Two recently identified human heparin-degrading endosulfatases, named sulfatase 1 (SULF1) and sulfatase 2 (SULF2), have been found to be involved in liver carcinogenesis. SULF1 and SULF2 desulfate cell surface and extracellular matrix heparan sulfate proteoglycans and modulate heparin-binding growth factor signaling in multiple cancers, including HCCs. SULF1 inhibits HCC tumor cell growth in vitro and in nude mice in vivo, partially through effects on gene expression mediated through histone H4 acetylation. While SULF1 is downregulated in the majority of HCC cell lines and approximately 30% of primary HCCs, SULF2 is upregulated in almost all HCC cell lines and in 60% of primary HCCs. In contrast to the tumor suppressor effect of SULF1, expression of SULF2 activates MAPK and Akt pathways, promotes HCC cell growth in vitro and in vivo, and is associated with decreased survival of HCC patients. Targeting SULF2 or the interaction between SULF2 and SULF1 may lead to novel therapeutics for the treatment of HCCs.

Original languageEnglish (US)
Pages (from-to)803-814
Number of pages12
JournalFuture Oncology
Volume4
Issue number6
DOIs
StatePublished - 2008

Keywords

  • Akt
  • Glypican 3
  • Heparan sulfate glycosaminoglycans
  • Heparan sulfate proteoglycan
  • Heparin-binding growth factor
  • Hepatocellular carcinoma
  • MAPK kinase
  • SULF1
  • SULF2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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