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Increased expression of transglutaminase 2 drives glycolytic metabolism in renal carcinoma cells

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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.

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Acknowledgments

This study was supported by a research Grant (NCC1410671-1) from the National Cancer Center of Korea to S.Y.K.

Conflict of interest

We declare that none of the authors have any financial interest related to this work, and none of the authors have any financial support beyond the research grant mentioned above.

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Authors and Affiliations

  1. Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Kyonggi-do, Republic of Korea

    Bo Mi Ku, Chang-Hun Lee, Seon-Hyeong Lee & Soo-Youl Kim

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  1. Bo Mi Ku
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  2. Chang-Hun Lee
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  3. Seon-Hyeong Lee
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  4. Soo-Youl Kim
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Correspondence to Soo-Youl Kim.

Additional information

B. M. Ku and C.-H. Lee contributed equally to this paper.

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Ku, B.M., Lee, CH., Lee, SH. et al. Increased expression of transglutaminase 2 drives glycolytic metabolism in renal carcinoma cells. Amino Acids 46, 1527–1536 (2014). https://doi.org/10.1007/s00726-014-1714-2

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  • DOI: https://doi.org/10.1007/s00726-014-1714-2

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