Ren 2014 Sci Rep
| Ren JG, Seth P, Clish CB, Lorkiewicz PK, Higashi RM, Lane AN, Fan TW, Sukhatme VP (2014) Knockdown of malic enzyme 2 suppresses lung tumor growth, induces differentiation and impacts PI3K/AKT signaling. Sci Rep 4:5414. doi: 10.1038/srep05414. |
Ren JG, Seth P, Clish CB, Lorkiewicz PK, Higashi RM, Lane AN, Fan TW, Sukhatme VP (2014) Sci Rep
Abstract: Mitochondrial malic enzyme 2 (ME2) catalyzes the oxidative decarboxylation of malate to yield CO2 and pyruvate, with concomitant reduction of dinucleotide cofactor NAD(+) or NADP(+). We find that ME2 is highly expressed in many solid tumors. In the A549 non-small cell lung cancer (NSCLC) cell line, ME2 depletion inhibits cell proliferation and induces cell death and differentiation, accompanied by increased reactive oxygen species (ROS) and NADP(+)/NADPH ratio, a drop in ATP, and increased sensitivity to cisplatin. ME2 knockdown impacts phosphoinositide-dependent protein kinase 1 (PDK1) and phosphatase and tensin homolog (PTEN) expression, leading to AKT inhibition. Depletion of ME2 leads to malate accumulation and pyruvate decrease, and exogenous cell permeable dimethyl-malate (DMM) mimics the ME2 knockdown phenotype. Both ME2 knockdown and DMM treatment reduce A549 cell growth in vivo. Collectively, our data suggest that ME2 is a potential target for cancer therapy.
Labels:
Pathology: Cancer
Tissue;cell: Lung;gill
Preparation: Intact cells
Malic enzyme
