Figure 6. A model of the metabolic stress response regulation by oncogenic BRAF in melanoma cells.

Resistance to stress conditions is essential for melanoma cells survival. We propose that oncogenic BRAF^V600E signaling (left panel) protects to apoptosis by regulating BH3-family members and confers resistance to low energy conditions promoting the uncoupling of LKB1 and AMPK through Erk1/2 and p90^Rsk. Under this condition BRAF mutant cells have a limited response to low energy conditions. On the right panel the inhibition of BRAF signaling allows the formation of the LKB1-AMPK complexes restoring the energy stress pathway and promoting the down-regulation of anti-apoptotic proteins such as Mcl1. The activation of AMPK by metabolic stress conditions and the inhibition of BRAF signaling would have synergistic effects promoting apoptosis.