Role of 2-O-sulfated and 3-O-sulfated heparan sulfate in breast cancer pathogenesis

V. Kumar/Götte demonstrated that ectopic expression of the heparan sulphate (HS) biosynthetic enzymes HS 3-O-sulfotransferase 2 (HS3ST2) and HS 2-O-sulfotransferase 1 (HS2ST1) differentially affects in vitro invasiveness, motility, and proliferation of human breast cancer cells. For HS3ST2, the phenotypic changes could be mechanistically linked to alterations in MAP kinase and Wnt-signaling. The resulting activation of the transcription factor TCF4 induced dysregulation of proteolytic factors and ion transporters linked to altered chemotherapeutic drug sensitivity. Similar observations were made for HS2ST1, where the stemness-associated Wnt-, Notch-, and HGF/c-Met-mediated signal transduction pathways were altered. Altered HS-ligand binding properties will be explored with Swamy and potential changes in cancer stem cell properties are studied with Suresh.

Last update 17.04.2013

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