Ren 2014 Sci Rep: Difference between revisions
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|journal=Sci Rep | |journal=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. | |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 | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Genetic knockout;overexpression | |||
|organism=Human | |||
|tissues=Lung;gill | |tissues=Lung;gill | ||
|model cell lines=Other cell lines | |||
|preparations=Intact cells | |preparations=Intact cells | ||
|diseases=Cancer | |diseases=Cancer | ||
|additional=Malic enzyme | |couplingstates=ROUTINE | ||
|additional=Malic enzyme | |||
}} | }} |
Revision as of 12:09, 20 October 2015
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. |
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. โข Keywords: Human lung cancer cell line A549
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Cancer
Organism: Human Tissue;cell: Lung;gill Preparation: Intact cells
Coupling state: ROUTINE
Malic enzyme