mTOR is an intracellular kinase that controls the production of proteins by regulating mRNA translation in response to environmental cues.^1,2 mTOR senses the availability of nutrients and consolidates this information with signaling from growth factors. Growth factor stimulation primarily stimulates mTOR signaling through the PI3K/Akt pathway, which is activated by growth factor receptors. Activated Akt mediates activation of mTOR.^2,3

 

Activated mTOR increases the rate of protein synthesis for certain mRNAs by activating proteins that direct DNA translation such as S6K1 and 4E-BP1.¹ This results in increased production of proteins that stimulate cell growth and proliferation, cellular metabolism, and angiogenesis.

• Growth and proliferation: mTOR increases translation of proteins that drive cell growth and cell division, such as cyclin D1, and decreases translation of negative regulators of cell cycle progression³
• Cell metabolism: mTOR increases the surface expression of nutrient transporters.² Increased availability of nutrients fulfills the energy, nutrient, and metabolic requirements for mTOR-activated cell growth and proliferation
• Angiogenesis: mTOR increases the translation of HIF (hypoxia inducible factor)-1α. The HIF transcription factors drive the expression of angiogenic growth factors such as VEGF, PDGF-β, and TGF-α⁴

mTOR acts as a central regulator that is frequently activated as a result of signaling from other proteins that are commonly mutated in cancer.²

 

mTOR supports cells with a supply of nutrients:
(1) mTOR activation increases the production of angiogenic growth factors; (2) increased blood vessel formation supplies the cellular environment with nutrients; (3) mTOR activation enhances nutrient uptake in the cell by increasing production of nutrient transporters; and (4) increased nutrient availability fulfills the metabolic needs for mTOR-mediated cell growth and proliferation.