More importantly, we identified that collagen/FN stimulated glioma progression through integrin αvβ3-induced PI3K/AKT/SOX2 and CDC42/F-actin/YAP-1/Nupr1/Nestin double signal activation simultaneously, expounding the underlying mechanism of the extracellular matrix-induced tumor signaling network. This evidence concerns the gene NES and central nervous system cancer.