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Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma

1
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
2
Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul 03722, Korea
3
Comparative Biomedicine Research Branch, Division of Translational Science, National Cancer Center, 323 Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5622; https://doi.org/10.3390/ijms20225622
Received: 7 October 2019 / Revised: 4 November 2019 / Accepted: 4 November 2019 / Published: 10 November 2019
(This article belongs to the Section Molecular Biology)
Emerging evidence indicates that the activity of pyruvate kinase M2 (PKM2) isoform is crucial for the survival of tumor cells. However, the molecular mechanism underlying the function of PKM2 in renal cancer is undetermined. Here, we reveal the overexpression of PKM2 in the proximal tubule of renal tumor tissues from 70 cases of patients with renal carcinoma. The functional role of PKM2 in human renal cancer cells following small-interfering RNA-mediated PKM2 knockdown, which retarded 786-O cell growth was examined. Targeting PKM2 affected the protein kinase B (AKT)/mechanistic target of the rapamycin 1 (mTOR) pathway, and downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, and other downstream signaling key proteins. PKM2 knockdown changed glycolytic metabolism, mitochondrial function, adenosine triphosphate (ATP) level, and intracellular metabolite formation and significantly reduced 786-O cell migration and invasion. Acridine orange and monodansylcadaverine staining, immunocytochemistry, and immunoblotting analyses revealed the induction of autophagy in renal cancer cells following PKM2 knockdown. This is the first study to indicate PKM2/AKT/mTOR as an important regulatory axis mediating the changes in the metabolism of renal cancer cells. View Full-Text
Keywords: pyruvate kinase M2; autophagy; metabolism; migration; invasion pyruvate kinase M2; autophagy; metabolism; migration; invasion
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Dey, P.; Son, J.Y.; Kundu, A.; Kim, K.S.; Lee, Y.; Yoon, K.; Yoon, S.; Lee, B.M.; Nam, K.T.; Kim, H.S. Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma. Int. J. Mol. Sci. 2019, 20, 5622.

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