Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Kyonggi-do, Republic of Korea.
Amino Acids. 2014 Jun;46(6):1527-36. doi: 10.1007/s00726-014-1714-2. Epub 2014 Mar 19.
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.
转谷氨酰胺酶 2（TGase 2）的表达和糖酵解在大多数肾细胞癌（RCC）细胞系中比 HEK293 肾细胞系增加。尽管糖酵解增加和三羧酸循环改变在 RCC 中很常见，但这种现象发生的详细机制仍有待阐明。在本研究中，TGase 2 siRNA 处理使 RCC 细胞中的葡萄糖消耗和乳酸水平降低约 20-30％；相反，高表达的 TGase 2 增加了葡萄糖消耗和乳酸生成，同时降低了线粒体顺乌头酸酶（Aco 2）水平。此外，TGase 2 siRNA 使 RCC 细胞中的线粒体膜电位和 ATP 水平增加约 20-30％，并恢复了 Aco 2 水平。同样，在 HEK293 细胞中转染 TGase 2 过表达后，Aco 2 水平和 ATP 产生显著下降。因此，TGase 2 导致 Aco 2 的耗竭，从而促进了 RCC 细胞的糖酵解代谢。
