Figure 6.

Proposed schematic. At the basal level, AKT works to stabilize BCA2 so that it is free to ubiquitinate protein substrates, including those controlling phosphorylation/dephosphorylation of AMPKα1 at Thr172, targeting them for degradation through the ubiquitin-proteasome pathway, resulting in inhibition of AMPK signaling in breast cancer cells. The activation of AMPK by metformin or AICAR, however, increases BCA2 protein levels, inciting a potential cancer cell survival involving PI3K/Akt. Therefore, the balance of AMPK and PI3K/AKT/BCA2 might control breast cancer cell sensitivity to metformin therapy and the tumor cell life-death switch.