Synergistic inhibition of NOTCH and ERG signaling reverses EMT. A&B, The concurrent inhibition of AR pathway and NOTCH signaling by GSI-1 and either Bicalutamide (Bic), or Enzalutamide (Enz) induces epithelial markers Claudin-1, E-Cadherin and β-Catenin, indicating activation of MET and inhibition of EMT. This might be responsible for the observed enhanced synergy between AR inhibitors and GSI-1. C&D, The proposed mechanism is that inhibition of AR’s tumor promoting function in combination with the pro-tumorigenic functions of NOTCH is more effective therapeutic approach than any of the compounds alone.