 The studies showed that decrease of ARSB leads to increase in free galectin-3, which attaches more strongly to less sulfated chondroitin 4-sulfate.Galectin-3 then acts on transcription factors AP-1 to increase expression of chondroitin sulfate proteoglycan versican and SP-1 to increase expression of WNT9A.Another mechanism by which reduced ARSB is associated with carcinogenesis is through increased binding of SHP2 to more sulfated chondroitin 4-sulfate, which leads to increased phosphorylation of p38 and MITF with subsequently increased expression of GPNMB.