Figure 7  YAP-mediated IGF2 expression drives cell survival, proliferation and genomic instability
Model suggesting the mechanism through which oncogenic YAP expression permits cell proliferation and survival after radiation-induced DNA damage. YAP induces IGF2 expression in CGNPs and medulloblastoma cells. IGF2 activates the PI3K/Akt pathway, promoting survival and increasing proliferation of these cells. In addition, increased activation of Akt leads to faster ATM and Chk2 dephosphorylation after radiation, subsequently deactivating the DNA damage response and removing the G1/S and G2/M checkpoints. Favoring survival, proliferation and genomic instability confers an advantage to YAP-expressing tumor cells. Inhibiting IGF2/Akt signaling in tumors with high YAP expression may prevent recurrence and enable use of lower radiation doses by increasing tumor cell radiosensitivity.