Figure 5.

The conflicting role of AMPK in glioma as a tumor suppressor and tumor promoter. Increased AMP: ATP and ADP: ATP ratios, metabolic stress and treatment with chemotherapy results in AMPK activation in glioma cells (Hardie and Alessi, 2013). This results in the activation of several downstream pathways that result in both tumor suppression and growth depending on the context of AMPK activation. Primarily AMPK activates p53 transcriptional activity leading to classical cell cycle inhibition, reducing tumor growth through p21^CIP1 and p27^KIP1 activation (Jones et al., 2005). AMPK activation also downregulates mTOR signaling resulting in decreased protein synthesis and G2 block, whilst also releasing its constraint on autophagy, increasing glioma survival during chemotherapy (Vucicevic et al., 2009; Misirkic et al., 2012). Unresolved stress over prolonged periods can also result in increased apoptosis and therefore decreased viability. By increasing Rb phosphorylation, AMPK activation is also able to overcome cell cycle inhibition (Ríos et al., 2014).