PIK3CA and osteosarcoma: Absent in melanoma 2 (AIM2) and Fer-1-like protein 4 (FER1L4) are two osteosarcoma inhibitors, and several studies have found that their overexpression inhibited the PI3K/AKT/mTOR signaling pathway, with an increase in E-calmodulin and a decrease in wave proteins and fibronectin, inhibiting EMT (Figure 3D) (61, 134).