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Gene Section Review Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST -CNRS Gene Section Review SULF1 (sulfatase 1) Jérôme Moreaux INSERM U1040, institut de recherche en biotherapie, CHRU Saint Eloi, 80 Av Augustain Fliche, 34295 Montpellier CEDEX 5, France (JM) Published in Atlas Database: March 2012 Online updated version : http://AtlasGeneticsOncology.org/Genes/SULF1ID44378ch8q13.html DOI: 10.4267/2042/47490 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology - Homo sapiens sulfatase 1 (SULF1), transcript variant Identity 3, mRNA, 5710 bp Other names: HSULF-1, SULF-1 Accession: NM_015170.2 GI: 189571635 HGNC (Hugo): SULF1 - Homo sapiens sulfatase 1 (SULF1), transcript variant 4, mRNA, 5548 bp Location: 8q13.2 Accession: NM_001128204.1 GI: 189571637 DNA/RNA Protein Note Note The sulfation pattern of heparan sulfate chains Sulfs are sulfatases that edit the sulfation status of influences signaling events mediated by heparan sulfate heparan sulfate proteoglycans on the outside of cells proteoglycans located on cell surface. SULF1 is an and regulate a number of critical signaling pathways. endosulfatase able to cleave specific 6-O sulfate groups The Sulfs are dysregulated in many cancers. within the heparan chains. The Sulfs are synthesized as pre-proproteins. This action can modulate signaling processes, The signal sequence is removed and the pro-protein is modulating the effects of heparan sulfate by altering cleaved by a furin-type proteinase. binding sites for signaling molecules. Sulfs mature proteins are secreted as well as retained Description on the cell surface. Size: 5551 bp. Description Transcription 871 amino acids; 101027 Da. 4 isoforms: Expression - Homo sapiens sulfatase 1 (SULF1), transcript variant Expressed at highest levels in testis, stomach, skeletal 1, mRNA, 5716 bp muscle, lung, kidney, pancreas, small intestine and Accession: NM_001128205.1 GI: 189571640 colon. - Homo sapiens sulfatase 1 (SULF1), transcript variant It is also detected in normal ovarian surface epithelial 2, mRNA, 5554 bp cells. Accession: NM_001128206.1 GI: 189571642 Adapted from Genecards. Atlas Genet Cytogenet Oncol Haematol. 2012; 16(8) 555 SULF1 (sulfatase 1) Moreaux J Localisation an aberrant hypermethylation of the Sulf1 promoter in breast cancer cell lines and patient samples, leading to a Sulfs mature proteins are secreted as well as retained reduction of Sulf1 expression. on the cell surface. Function Hepatocellular carcinoma Oncogenesis The Sulfs are endoglucosamine-6-sulfatases. They liberate 6-O-S mainly from trisulfated disaccharide Sulf1 expression was also found to be significantly units within the S-domains of heparin/HS chains. The downregulated in hepatocellular carcinoma. Sulfs have been shown to modulate the interaction of a It has also been observed that this down-regulation number of protein ligands with heparin or heparan results in increased sulfation of heparin sulfate chains sulfate. and could produce the stabilization of ternary receptor complexes, leading to an increased in growth factors Homology signaling. SULF1 shares about 64% identity with SULF2. Forced expression of SULF1 also significantly delayed the growth of hepatocellular carcinoma cell lines Implicated in xenografts in nude mice. Sulf1 enhances acetylation of histone H4 by inhibiting Ovarian cancer HDAC, which subsequently decreased hepatocellular Oncogenesis carcinoma cell tumorogenesis in mouse model. Sulf1 expression was found to be absent or Pancreatic cancer significantly downregulated in ovarian cancer resulting Oncogenesis in highly sulfated heparin sulfate proteoglycans. Hsulf-1-mediated desulphation of HSPGs reduces the It has been observed that this down-regulation results in growth ability of pancreatic cancer cells, but increases increased sulfation of heparin sulfate chains and could the basal invasiveness of these cells and produce the stabilization of ternary receptor complexes, chemoresistance, suggesting an important role of this leading to an increased in GF signaling, as described enzyme in pancreatic cancer progression. Recent for heparin-binding epidermal growth factor-like analysis using microarray data demonstrated a growth factor (HB-EGF), fibroblast growth factor 2 significant upregulation of Sulf1 in pancreatic (FGF2) or amphiregulin in ovarian cancer. adenocarinoma compared to normal counterpart. This modulation of GF effects can affect major events including proliferation of tumor cells. Epigenetic Head and neck squamous cell silencing by methylation is associated with ovarian carcinoma cancer cells and primary ovarian cancer tissues lacking Oncogenesis Sulf1 expression. Sulf1 expression was also found to be significantly Cisplatin-induced apoptosis of the ovarian cancer cell downregulated in head and neck squamous cell line, OV207, requires Sulf1 activity. carcinoma cell lines. Breast cancer It has also been observed that this down-regulation Oncogenesis results in increased sulfation of heparin sulfate chains Sulf1 expression was first described to be significantly and could produce the stabilization of ternary receptor downregulated in breast cancer. Recent analysis using complexes, leading to an increased in growth factors microarray data demonstrated a significant signaling in head and neck squamous cell carcinoma upregulation of Sulf1 in breast cancer compared to cell lines. normal counterpart. Hepatocyte growth factor (HGF)-mediated motility and It has been observed that this down-regulation results in invasion were attenuated in neck squamous cell increased sulfation of heparin sulfate chains and could carcinoma cell lines displaying an overexpression of produce the stabilization of ternary receptor complexes, this sulfatase. leading to an increased in growth factors signaling, as However, recent analysis using microarray data described for heparin-binding epidermal growth factor- demonstrated a significant upregulation of Sulf1 in like growth factor (HB-EGF), fibroblast growth factor head and neck squamous cell carcinoma compared to 2 (FGF2) or amphiregulin in breast cancer. normal counterpart. This modulation of GF effects can affect major events Leukemia including proliferation of tumor cells. Oncogenesis A marked reduction of the growth of myeloma or Recent analysis using microarray data demonstrated a breast cancer cell lines was observed in severe significant upregulation of Sulf1 in leukemia compared combined immunodeficient mice when injected cell to normal counterpart. lines were transfected with SULF1 cDNA. It was found Atlas Genet Cytogenet Oncol Haematol. 2012; 16(8) 556 SULF1 (sulfatase 1) Moreaux J Gastric cancer Renal carcinoma Oncogenesis Oncogenesis Promoter hypermethylation is correlated with the Recent analysis using microarray data demonstrated a HSulf-1 silencing in gastric cancer. significant upregulation of Sulf1 in renal carcinoma The restoration of the expression of HSulf-1 inhibited compared to normal counterpart. cell proliferation, motility, and invasion of the MKN28 Sarcoma cell line in vitro, as well as in a xenograft mouse model. Oncogenesis No noticeable changes in proliferation and motility Recent analysis using microarray data demonstrated a were observed following restoration of HSulf-1 in significant upregulation of Sulf1 in sarcoma compared another gastric cancer cell line AGS. to normal counterpart. HSulf-1 function as a negative regulator of Melanoma proliferation and invasion in MKN28 gastric cancer Oncogenesis cell line by suppressing Wnt/ β-catenin signaling. However, as for others cancers, recent analysis using Recent analysis using microarray data demonstrated a microarray data demonstrated a significant significant upregulation of Sulf1 in cutaneous upregulation of Sulf1 in leukemia compared to normal melanoma compared to normal skin. counterpart. Testicular cancer Colon cancer Oncogenesis Oncogenesis Recent analysis using microarray data demonstrated a Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in testicular cancer significant upregulation of Sulf1 in colon cancer compared to normal counterpart. compared to normal counterpart. References Adrenal cancer Galeazzi E, Olivero M, Gervasio FC, De Stefani A, Valente G, Oncogenesis Comoglio PM, Di Renzo MF, Cortesina G. Detection of MET Recent analysis using microarray data demonstrated a oncogene/hepatocyte growth factor receptor in lymph node significant upregulation of Sulf1 in adrenal cancer metastases from head and neck squamous cell carcinomas. Eur Arch Otorhinolaryngol. 1997;254 Suppl 1:S138-43 compared to normal counterpart. Lundin L, Larsson H, Kreuger J, Kanda S, Lindahl U, Salmivirta Esophageal cancer M, Claesson-Welsh L. Selectively desulfated heparin inhibits Oncogenesis fibroblast growth factor-induced mitogenicity and angiogenesis. J Biol Chem. 2000 Aug 11;275(32):24653-60 Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in esophageal cancer Dong G, Chen Z, Li ZY, Yeh NT, Bancroft CC, Van Waes C. Hepatocyte growth factor/scatter factor-induced activation of compared to normal counterpart. MEK and PI3K signal pathways contributes to expression of Lung cancer proangiogenic cytokines interleukin-8 and vascular endothelial growth factor in head and neck squamous cell carcinoma. Prognosis Cancer Res. 2001 Aug 1;61(15):5911-8 In a cohort of 127 patients with lung adenocarcinoma,
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