Interplay between Mitochondrial Metabolism and Cellular Redox State Dictates Cancer Cell Survival

Figure 2

ROS regulation of signaling pathways in cancer. ROS has been demonstrated to regulate signaling pathways in cancer. Increase in ROS such as H₂O₂ activates PI3K/Akt signaling pathway through the inhibition of PTEN, resulting in constitutive activation of PI3K/Akt that contributes to cell survival and proliferation in cancer. Similarly, ASK-1, a kinase in the MAPK signaling cascade, is displaced from Trx-ASK1 complex under oxidative stress. ASK-1 subsequently activates downstream p38 and JNK, leading to apoptosis and autophagy. Redox-mediated inactivation of PP2A was reported to sustain NF-κB activation, Bcl-2 phosphorylation at Ser70, and Myc phosphorylation at Ser62, leading to cell migration and invasion, inhibition of DNA damage and cell proliferation, respectively. Figure created with biorender.com.