Institut de Biologie StructuraleGrenoble / France

Extracellular endosulfatase HSulf-2 harbours a polysaccharide chain that muzzles its pro-tumoral activity

Polysaccharides of the Glycosaminoglycans (GAGs) family are essential components of cell surfaces and interstitial matrices. Among them, heparan sulfates (HS) are involved in a large number of biological functions, thanks to their ability to bind and regulate a wide array of signaling proteins. These mechanisms are tightly controlled by extracellular enzymes such as HSulf-2 endosulfatase, which modify the structure of HS and their interaction properties.
Researchers from IBS (Structure and activity of Glycosaminoglycans, Vivès team) and CEA-Biosanté (IMAC team, Odile Filhol-Cochet) have shown that HSulf-2 itself carries a GAG chain that acts as a modulator of its activity. As such, its removal (by mutation or enzymatic digestion) significantly increases the activity of the enzyme in vitro, and overexpression of Sulf-2 without a GAG chain in breast cancer cells promotes cell proliferation, migration and invasion, but also tumor growth and lung metastasis in vivo (figure).
This work sheds new light on the regulation of HS by HSulf-2, and for the development of antitumor strategies targeting these enzymes.

Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity. El Masri R, Seffouh A, Roelants C, Seffouh I, Gout E, Pérard J, Dalonneau F, Nishitsuji K, Noborn F, Nikpour M, Larson G, Crétinon Y, Friedel-Arboleas M, Uchimura K, Daniel R, Lortat-Jacob H, Filhol O, Vivès RR. Cell Reports ; 38(11):110516

Contact : Romain Vivès (IBS/Structure and Activity of Glycosaminoglycans Group)