Ren 2014 Sci Rep

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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.

» PMID: 24957098 Open Access

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.

Keywords: Human lung cancer cell line A549


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Cancer 

Organism: Human  Tissue;cell: Lung;gill, Other cell lines  Preparation: Intact cells 


Coupling state: ROUTINE 


Malic enzyme