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Journal of Gastrointestinal Cancer

Published in:

01-03-2008

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

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

Published in: Journal of Gastrointestinal Cancer | Issue 1-4/2008

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.

Diez-Roux G, Ballabio A. Sulfatases and human disease. Annu Rev Genomics Hum Genet. 2005;6:355–79. doi:10.1146/annurev.genom.6.080604.162334.PubMedCrossRef

Shridhar V, Sen A, Chien J, Staub J, Avula R, Kovats S, et al. Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization. Cancer Res. 2002;62 1:262–70.PubMed

Ai X, Do AT, Kusche-Gullberg M, Lindahl U, Lu K, Emerson CP Jr. Substrate specificity and domain functions of extracellular heparan sulfate 6-O-endosulfatases, QSulf1 and QSulf2. J Biol Chem. 2006;281 8:4969–76. doi:10.1074/jbc.M511902200.PubMedCrossRef

Dhoot GK, Gustafsson MK, Ai X, Sun W, Standiford DM, Emerson CP Jr. Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science. 2001;293 5535:1663–6. doi:10.1126/science.293.5535.1663.PubMedCrossRef

Lai J, Chien J, Staub J, Avula R, Greene EL, Matthews TA, et al. Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer. J Biol Chem. 2003;278 25:23107–17. doi:10.1074/jbc.M302203200.PubMedCrossRef

Lai JP, Chien JR, Moser DR, Staub JK, Aderca I, Montoya DP, et al. hSulf1 sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing heparin-binding growth factor signaling. Gastroenterology. 2004;126 1:231–48. doi:10.1053/j.gastro.2003.09.043.PubMedCrossRef

Forsten-Williams K, Chu CL, Fannon M, Buczek-Thomas JA, Nugent MA. Control of growth factor networks by heparan sulfate proteoglycans. Ann Biomed Eng. 2008;36 12:2134–48. doi:10.1007/s10439-008-9575-z.PubMedCrossRef

Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, et al. Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1999;6 3:197–205. doi:10.1093/dnares/6.3.197.PubMedCrossRef

Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD. Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. J Biol Chem. 2002;277 51:49175–85. doi:10.1074/jbc.M205131200.PubMedCrossRef

10.

Ohto T, Uchida H, Yamazaki H, Keino-Masu K, Matsui A, Masu M. Identification of a novel nonlysosomal sulphatase expressed in the floor plate, choroid plexus and cartilage. Genes Cells. 2002;7 2:173–85. doi:10.1046/j.1356-9597.2001.00502.x.PubMedCrossRef

11.

Staub J, Chien J, Pan Y, Qian X, Narita K, Aletti G, et al. Epigenetic silencing of HSulf-1 in ovarian cancer: implications in chemoresistance. Oncogene. 2007;26 34:4969–78. doi:10.1038/sj.onc.1210300.PubMedCrossRef

12.

Lai JP, Chien J, Strome SE, Staub J, Montoya DP, Greene EL, et al. HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma. Oncogene. 2004;23 7:1439–47. doi:10.1038/sj.onc.1207258.PubMedCrossRef

13.

Narita K, Chien J, Mullany SA, Staub J, Qian X, Lingle WL, et al. Loss of HSulf-1 expression enhances autocrine signaling mediated by amphiregulin in breast cancer. J Biol Chem. 2007;282 19:14413–20. doi:10.1074/jbc.M611395200.PubMedCrossRef

14.

Li J, Kleeff J, Abiatari I, Kayed H, Giese NA, Felix K, et al. Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer. Mol Cancer. 2005;4 1:14. doi:10.1186/1476-4598-4-14.PubMedCrossRef

15.

Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M, Rosen SD. Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS ONE. 2007;2 4:e392. doi:10.1371/journal.pone.0000392.PubMedCrossRef

16.

Soule HD, Maloney TM, Wolman SR, Peterson WD Jr, Brenz R, McGrath CM, et al. Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res. 1990;50 18:6075–86.PubMed

17.

Cross SH, Charlton JA, Nan X, Bird AP. Purification of CpG islands using a methylated DNA binding column. Nat Genet. 1994;6 3:236–44. doi:10.1038/ng0394-236.PubMedCrossRef

18.

Chen Z, Fan JQ, Li J, Li QS, Yan Z, Jia XK, et al. Promoter hypermethylation correlates with the Hsulf-1 silencing in human breast and gastric cancer. Int J Cancer. 2009;124 3:739–44. doi:10.1002/ijc.23960.PubMedCrossRef

19.

Ai X, Do AT, Lozynska O, Kusche-Gullberg M, Lindahl U, Emerson CP Jr. QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. J Cell Biol. 2003;162 2:341–51. doi:10.1083/jcb.200212083.PubMedCrossRef

20.

Lundin L, Larsson H, Kreuger J, Kanda S, Lindahl U, Salmivirta M, et al. Selectively desulfated heparin inhibits fibroblast growth factor-induced mitogenicity and angiogenesis. J Biol Chem. 2000;275 32:24653–60. doi:10.1074/jbc.M908930199.PubMedCrossRef

21.

Delehedde M, Lyon M, Gallagher JT, Rudland PS, Fernig DG. Fibroblast growth factor-2 binds to small heparin-derived oligosaccharides and stimulates a sustained phosphorylation of p42/44 mitogen-activated protein kinase and proliferation of rat mammary fibroblasts. Biochem J. 2002;366 Pt 1:235–44.PubMed

22.

Wang S, Ai X, Freeman SD, Pownall ME, Lu Q, Kessler DS, et al. QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis. Proc Natl Acad Sci USA. 2004;101 14:4833–8. doi:10.1073/pnas.0401028101.PubMedCrossRef

23.

Dong G, Chen Z, Li ZY, Yeh NT, Bancroft CC, Van Waes C. Hepatocyte growth factor/scatter factor-induced activation of MEK and PI3K signal pathways contributes to expression of proangiogenic cytokines interleukin-8 and vascular endothelial growth factor in head and neck squamous cell carcinoma. Cancer Res. 2001;61 15:5911–8.PubMed

24.

Dong G, Lee TL, Yeh NT, Geoghegan J, Van Waes C, Chen Z. Metastatic squamous cell carcinoma cells that overexpress c-Met exhibit enhanced angiogenesis factor expression, scattering and metastasis in response to hepatocyte growth factor. Oncogene. 2004;23 37:6199–208. doi:10.1038/sj.onc.1207851.PubMedCrossRef

25.

Matsumoto K, Matsumoto K, Nakamura T, Kramer RH. Hepatocyte growth factor/scatter factor induces tyrosine phosphorylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells. J Biol Chem. 1994;269 50:31807–13.PubMed

26.

Galeazzi E, Olivero M, Gervasio FC, De Stefani A, Valente G, Comoglio PM, et al. Detection of MET oncogene/hepatocyte growth factor receptor in lymph node metastases from head and neck squamous cell carcinomas. Eur Arch Otorhinolaryngol. 1997;254 Suppl 1:S138–43. doi:10.1007/BF02439745.PubMedCrossRef

27.

Narita K, Staub J, Chien J, Meyer K, Bauer M, Friedl A, et al. HSulf-1 inhibits angiogenesis and tumorigenesis in vivo. Cancer Res. 2006;66 12:6025–32. doi:10.1158/0008-5472.CAN-05-3582.PubMedCrossRef

28.

Lai JP, Yu C, Moser CD, Aderca I, Han T, Garvey TD, et al. SULF1 inhibits tumor growth and potentiates the effects of histone deacetylase inhibitors in hepatocellular carcinoma. Gastroenterology. 2006;130 7:2130–44. doi:10.1053/j.gastro.2006.02.056.PubMedCrossRef

29.

Lai J-P, Sandhu D, Moser C, Cazanave S, Oseini A, Shire A, Shridhar V, Sanderson S, Roberts L. Additive effect of apicidin and doxorubicin in sulfatase 1 (SULF1)-expressing hepatocellular carcinoma in vitro and in vivo. J Hepatol. 2009; in press.

30.

Abiatari I, Kleeff J, Li J, Felix K, Buchler MW, Friess H. Hsulf-1 regulates growth and invasion of pancreatic cancer cells. J Clin Pathol. 2006;59 10:1052–8. doi:10.1136/jcp.2005.031716.PubMedCrossRef

31.

Dai Q, Qian SB, Li HH, McDonough H, Borchers C, Huang D, et al. Regulation of the cytoplasmic quality control protein degradation pathway by BAG2. J Biol Chem. 2005;280 46:38673–81. doi:10.1074/jbc.M507986200.PubMedCrossRef

32.

Butler KV, Kozikowski AP. Chemical origins of isoform selectivity in histone deacetylase inhibitors. Curr Pharm Des. 2008;14 6:505–28. doi:10.2174/138161208783885353.PubMedCrossRef

33.

Lamanna WC, Baldwin RJ, Padva M, Kalus I, Ten Dam G, van Kuppevelt TH, et al. Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity. Biochem J. 2006;400 1:63–73. doi:10.1042/BJ20060848.PubMedCrossRef

34.

Lamanna WC, Frese MA, Balleininger M, Dierks T. Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling. J Biol Chem. 2008;283 41:27724–35. doi:10.1074/jbc.M802130200.PubMedCrossRef

Title: The Tumor Suppressor Function of Human Sulfatase 1 (SULF1) in Carcinogenesis
Authors: Jin-Ping Lai
Dalbir S. Sandhu
Abdirashid M. Shire
Lewis R. Roberts
Publication date: 01-03-2008
Publisher: Humana Press Inc
Published in: Journal of Gastrointestinal Cancer / Issue 1-4/2008
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI: https://doi.org/10.1007/s12029-009-9058-y

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Abstract

Introduction

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