Fig. 8. BMX bypasses SOCS3 negative regulation on JAK2 to sustainably activate STAT3 in GSCs.

(A) Immunoblot analyses of pBMX-Y⁴⁰, BMX, pSTAT3-Y⁷⁰⁵, STAT3, SOCS3, and tubulin in D456 GSCs transduced with SOCS3 or the control vector upon IL-6 stimulation. (B) Coimmunoprecipitation of BMX with anti-SOCS3 antibody in D456 GSCs upon IL-6 stimulation. Precipitation with normal mouse IgG was used as a negative control. Total cell lysates (input) were immunoblotted with antibodies against SOCS3, BMX, and GAPDH. (C) In vitro cell viability analyses of human GSCs (D456) and NPCs (15167) expressing SOCS3 or the control vector. (D) Schematic diagram of targeting GSCs through BMX inhibition by ibrutinib and the underlying molecular mechanisms. BMX bypasses the SOCS3-mediated inhibition of JAK2 to sustain activation of STAT3 in GSCs (left), whereas JAK2-mediated STAT3 activation in NPCs (right) is negatively regulated by SOCS3, providing a molecular basis for targeting BMX by ibrutinib to specifically inhibit STAT3 activation in GSCs but not in NPCs. The symbol (‘) means minutes. Statistical analysis was performed using unpaired Student’s t test. Data are means ± SD. **P < 0.01.