Figure 4.

Intracellular mechanisms promoting proliferation in GBM. Growth factors, chemokine ligands, and other upstream signals upregulate the Ras/Raf/MEK/ERK and PI3K/Akt pathways. Downstream effectors, including HIF-1, EGFR, NF-κB, and mTOR, promote DNA synthesis, transcription, and tumor cell proliferation. Proliferative effectors notably engage in crosstalk with other signals in GBM, including those for angiogenesis (HIF-1), cell cycle progression (Akt), metabolism (Akt), motility (PI3K), apoptosis (Akt/mTOR), and autophagy (Akt/mTOR/Beclin-1).