Importance Of The Field: Sulf-1 and Sulf-2 are sulfatases that edit the sulfation status of heparan sulfate proteoglycans (HSPGs) on the outside of cells and regulate a number of critical signaling pathways. The Sulfs are dysregulated in many cancers with Sulf-2 in particular implicated as a driver of carcinogenesis in NSCLC, pancreatic cancer and hepatocellular carcinoma.
Areas Covered In This Review: This review describes the novel activity of the Sulfs in altering the sulfation pattern of HSPG chains on the outside of cells. Thereby, the Sulfs can change the binding of growth factors to these chains and can either promote (e.g., Wnt) or inhibit (e.g., fibroblast growth factor-2) signaling. The review focuses on the widespread upregulation of both Sulfs in cancers and summarizes the evidence that Sulf-2 promotes the transformed behavior of several types of cancer cells in vitro as well as their tumorigenicity in vivo.
What The Reader Will Gain: Sulf-2 is a bonafide candidate as a cancer-causing agent in NSCLC and other cancers in which it is upregulated.
Take Home Message: Sulf-2 is an extracellular enzyme and as such would be an attractive therapeutic target for the treatment of NSCLC and other cancers.
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http://dx.doi.org/10.1517/14728222.2010.504718 | DOI Listing |
Mol Cell Proteomics
July 2024
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA; Clinical and Translational Glycoscience Research Center, Georgetown University, Washington, District of Columbia, USA; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, District of Columbia, USA.
Human extracellular 6-O-endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6-O sulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented, and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). Despite its importance, limited information is available on direct protein-protein interactions of the Sulf-2 protein in the tumor microenvironment.
View Article and Find Full Text PDFbioRxiv
December 2023
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Human extracellular 6--endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6- sulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). In spite of its importance, limited information is available on direct protein-protein interactions of the Sulf-2 protein in the tumor microenvironment.
View Article and Find Full Text PDFUnlabelled: Membrane-associated heparan sulfate (HS) proteoglycans (PGs) contribute to the regulation of extracellular cellular signaling cues, such as growth factors (GFs) and chemokines, essential for normal organismal functions and implicated in various pathophysiologies. PGs accomplish this by presenting high affinity binding sites for GFs and their receptors through highly sulfated regions of their HS polysaccharide chains. The composition of HS, and thus GF-binding specificity, are determined during biosynthetic assembly prior to installation at the cell surface.
View Article and Find Full Text PDFGlycobiology
June 2023
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, United States.
Sulf-2 is an extracellular heparan 6-O-endosulfatase involved in the postsynthetic editing of heparan sulfate (HS), which regulates many important biological processes. The activity of the Sulf-2 and its substrate specificity remain insufficiently characterized in spite of more than two decades of studies of this enzyme. This is due, in part, to the difficulties in the production and isolation of this highly modified protein and due to the lack of well-characterized synthetic substrates for the probing of its catalytic activity.
View Article and Find Full Text PDFCell Mol Immunol
October 2022
Department of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, WA, USA.
Extracellular sulfatase-2 (Sulf-2) influences receptor-ligand binding and subsequent signaling by chemokines and growth factors, yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis (RA). In the present study, we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts (RASFs). Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg mice.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!