Extracellular sulfatase Sulf-2 (SULF2)

Extracellular sulfatase Sulf-2 (SULF2) is an enzyme that modifies the sulfation patterns of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix and on the cell surface [1, 8]. It specifically removes 6-O-sulfate groups from glucosamine residues, a process that regulates the interaction between HSPGs and various signaling molecules [2, 7]. This enzymatic activity promotes the mobilization and activation of growth factors such as Wnt, FGF, and VEGF, which are critical for tumor growth and survival [13, 16]. SULF2 is frequently overexpressed in several aggressive malignancies, including hepatocellular carcinoma, non-small cell lung cancer, and pancreatic cancer, where it acts as an oncogenic driver [2, 19, 20]. Beyond its role in cancer, SULF2 is implicated in the progression of liver fibrosis and cirrhosis by modulating TGF-beta signaling and fibroblast activation [4, 11]. Therapeutic strategies targeting SULF2 include small molecule inhibitors and monoclonal antibodies designed to block its catalytic activity and disrupt downstream oncogenic signaling [18, 21]. Clinical candidates like OKN-007 are currently being evaluated for their ability to inhibit SULF2 and sensitize tumors to other therapies [18]. As a secreted enzyme, SULF2 also serves as a potential serum biomarker for the early detection and prognosis of various cancers and chronic liver diseases [20, 22].

Other names

HSULF-2hSulf-2Sulfatase 2ArylsulfataseN-acetylglucosamine-6-sulfataseKIAA1247

Inhibition of 6-O-endosulfatase activity, leading to the disruption of growth factor mobilization (e.g., Wnt, FGF, VEGF) and subsequent inhibition of oncogenic signaling pathways such as PI3K/Akt and MAPK.