title: Increased expression of transglutaminase 2 drives glycolytic metabolism in renal carcinoma cells.
abstract: Transglutaminase 2 (TGase 2) expression and glycolysis are increased in most renal cell carcinoma (RCC) cell lines compared to the HEK293 kidney cell line. Although increased glycolysis and altered tricarboxylic acid cycle are common in RCC, the detailed mechanism by which this phenomenon occurs remains to be elucidated. In the present study, TGase 2 siRNA treatment lowered glucose consumption and lactate levels by about 20-30 % in RCC cells; conversely, high expression of TGase 2 increased glucose consumption and lactate production together with decreased mitochondrial aconitase (Aco 2) levels. In addition, TGase 2 siRNA increased mitochondrial membrane potential and ATP levels by about 20-30 % and restored Aco 2 levels in RCC cells. Similarly, Aco 2 levels and ATP production decreased significantly upon TGase 2 overexpression in HEK293 cells. Therefore, TGase 2 leads to depletion of Aco 2, which promotes glycolytic metabolism in RCC cells.
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Kyonggi-do, Republic of Korea.
authors.forename: Bo Mi
authors.initials: BM
authors.lastname: Ku
authors.forename: Chang-Hun
authors.initials: CH
authors.lastname: Lee
authors.forename: Seon-Hyeong
authors.initials: SH
authors.lastname: Lee
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000154:Aconitate Hydratase / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology*; D053078:Membrane Potential, Mitochondrial; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
chemical_list: D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019204:GTP-Binding Proteins; C476079:ACO2 protein, human; D000154:Aconitate Hydratase; C497446:VHL protein, human; D005947:Glucose