GNMT is a tumor suppressor for hepatocellular carcinoma (HCC). We found that DEPTOR, a novel mTOR binding protein, interacts with GNMT through its PDZ domain. DEPTOR expression is significantly increased in HCC, especially among patients with HCV infection. Loss of DEPTOR in HuH-7 cells activates S6K but reduces Akt activation and cell growth. DEPTOR overexpression activates Akt and extends survival of HCC cells. Overexpression of GNMT counteracts DEPTOR induced Akt activation and activates mTORC1 downstream signaling via disruption of the DEPTOR-mTOR interaction. Moreover, GNMT overexpression delays G2/M progression, which causes senescence and slows proliferation of HuH-7 cells, sensitizing them to rapamycin. We suggest that GNMT by interacting with DEPTOR regulates the cellular homeostasis of hepatocytes through modulation of Akt/mTORC1 signaling.
Date:
2011-04
Relation:
Cancer Research. 2011 Apr;71(Suppl. 8):Meeting Abstract 1990.
