In contrast, SHP2 binds more tightly with more highly sulfated C4S when ARSB is reduced, leading to sustained ERK1/2, JNK, or p38-MAPK phosphorylation and increased expression of pro-MMP-2 in melanoma [33], EGFR in prostate [28], CHST15 (carbohydrate sulfotransferase 15; N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase) in prostate [38], MITF (melanocyte inducing transcription factor) in liver [14], and enhanced promoter methylation with decline in expression of DKK3 (Dickkopf Wnt signaling pathway inhibitor) in prostate [36,37]. The gene discussed is PTPN11; the disease is melanoma.