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

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.

Pyruvate kinase M2 (PKM2) improve symptoms of post‐ischemic stroke depression by activating VEGF to mediate the MAPK/ERK pathway

“…Recently, the relationship between PKM2 and SIRT5 was confirmed to prevent colitis in mice (Wang et al., 2017). Moreover, PKM2 was found to ameliorate cell proliferation, metabolism, and migration in renal cell carcinoma (Dey et al., 2019). Due to multi‐targeted actions of PKM2, it could have broad prospects in the development of new and safe drugs as a promising cytosolic enzyme.…”

Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells

“…Western blot analysis was performed as previously described [ 25 ]. The 786-O cells were treated with the indicated concentration of the small molecule for 48 h. Cells were harvested and the whole cell lysate was prepared using the PRO-PREP cell lysis buffer.…”

Intratumoral Fibrosis in Facilitating Renal Cancer Aggressiveness: Underlying Mechanisms and Promising Targets

“…As an intermediate regulator, a wide range of molecules contribute to RCC different malignant phenotypes via mTOR signaling pathway, including pyruvate kinase M2 (PKM2) ( Dey et al, 2019 ), enoyl-CoA hydratase short-chain 1 (ECHS1) ( Qu et al, 2020 ), nucleobindin-2 (NUCB-2) ( Tao et al, 2020 ), miR-100 ( Liu et al, 2020b ), and maternal and embryonic leucine zipper kinase (MELK) ( Zhang et al, 2019 ). Mutations in upstream factors of mTOR signaling pathway were also involved.…”