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Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 22, International Journal of Molecular Sciences, Vol 20, Iss 22, p 5622 (2019)
- Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Male
Apoptosis
migration
lcsh:Chemistry
Cell Movement
Tumor Cells, Cultured
Glycolysis
lcsh:QH301-705.5
Spectroscopy
Aged, 80 and over
education.field_of_study
Chemistry
General Medicine
Middle Aged
Prognosis
invasion
Kidney Neoplasms
Computer Science Applications
Cell biology
Gene Expression Regulation, Neoplastic
Female
Adult
Thyroid Hormones
autophagy
Lactate dehydrogenase A
PKM2
Catalysis
Article
Inorganic Chemistry
Biomarkers, Tumor
Humans
Physical and Theoretical Chemistry
education
Molecular Biology
Protein kinase B
Carcinoma, Renal Cell
PI3K/AKT/mTOR pathway
Aged
Cell Proliferation
Cell growth
Organic Chemistry
Membrane Proteins
lcsh:Biology (General)
lcsh:QD1-999
Case-Control Studies
Cancer cell
pyruvate kinase M2
Carrier Proteins
metabolism
Pyruvate kinase
Follow-Up Studies
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 20
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....60f0ae4a019e07d2d84a5223e31a6c36