PI3K/AKT/mTOR pathway and c-Myc inhibit hepatocyte suspension under simulated microgravity

Microgravity affects cell growth and apoptosis. Using a random positioning machine, we previously found that simulated microgravity (SMG) suppresses total cell proliferation and induces apoptosis of in vitro cultured hepatocytes. Here, we report an interesting finding that SMG partially suspends these hepatocytes, forming large spheroids. Both attached and suspended cells can grow, but suspended cells exhibit reduced cell growth and apoptosis, implying dormancy. Mechanistically, attached but not suspended cells exhibit upregulated PI3K/AKT/mTOR pathway activity and downstream protein c-Myc. Knocking down c-Myc promotes, whereas overexpressing it suppresses, hepatocyte suspension under SMG, suggesting that the PI3K/AKT/mTOR pathway and c-Myc protect these cells from entering a dormant state upon SMG.