Figure 5.

Schematic representation of the effects of enforced expression of RAGE in TE671 ERMS cells. RAGE engaged by HMGB1 stimulates myogenic differentiation through activation of MKK6/p38 MAPK and myotube hypertrophy through PI3‐K/Akt. HMGB1/RAGE‐dependent activation of p38 MAPK also causes inactivation of ERK1/2 and JNK with consequent inhibition of proliferation and decrease in cell survival. Induction of RAGE in ERMS cells also results in the expression of myogenin and MyoD so as to cause repression of PAX7 expression and PAX7 proteasomal degradation, ultimately leading to reduction of proliferation, enhancement of apoptosis, and myogenic differentiation. Finally, the reduction of Pax7 expression by the RAGE/myogenin axis causes a reduction of cell migration and invasiveness in ERMS.