Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients

Abstract

The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (HK2, PFKM, and PKM2) were assessed in the breast cancer cohort of Pakistan using quantitative polymerase chain reaction (qPCR) and IHC. Expression patterns were correlated with molecular subtypes and clinical parameters in the patients. A significant upregulation of key glycolytic genes was observed in tumor samples in comparison to their adjacent controls (p < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (p < 0.05). HK2 and PKM2 were found to be upregulated in luminal B, whereas PFKM was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker Ki67 (p < 0.001). Moreover, moderate positive linear correlations between HK2 and PKM2 (r = 0.476), HK2 and PFKM (r = 0.473), and PKM2 and PFKM (r = 0.501) were also observed (p < 0.01). These findings validate that the key regulatory genes in glycolysis can serve as potential biomarkers and/or molecular targets for breast cancer management. However, the clinical significance of these molecules needs to be further validated through in vitro and in vivo experiments.

High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System

“…A dynamic metabolic shift in the NPCs was also observed in our data in which, at higher doses of CBD (5 µM), a decrease in glycolysis and an increase in β-oxidation were favored, mainly from the early to the nal stages of metabolic pathways. Enzymes such as hexokinase and pyruvate kinase play an essential role in the glycolytic pathway as both enzymes are allosterically regulated, which means they can regulate glycolysis (Ishfaq et al 2022). Therefore, the decrease of HK2 and PKM2 expression observed in our study at higher concentrations of CBD can be interpreted as the allosteric regulation of both enzymes due to the lower presence of glucose.…”

Icariin ameliorates glycolytic dysfunction in Alzheimer's disease models by activating the Wnt/β‐catenin signaling pathway

“…In vitro study, we observed decreased protein levels and activities of HK1 and PKM1 in the HT22 cells injured by Ab 25-35 , which were increased after ICA treatment; while the expression and activity of PFKM1 were not significantly different in all groups of HT22 cells, which was slightly different from the results of vivo experiments. The disparity in PFKM1 protein and activity levels between in vivo and in vitro conditions may be attributed to the influence of factors such as exercise, diet (specifically high fructose intake), age, and disease on in vivo experiments [53][54][55], which are absent from in vitro studies. However, the exact mechanism is still not fully discovered and there are other possible reasons for the difference, all of which need to be further investigated.…”

ATAD2 promotes glycolysis and tumor progression in clear cell renal cell carcinoma by regulating the transcriptional activity of c-Myc

“…HK2 is a hexokinase that participates in glycolysis and is essential for the Warburg effect. HK2 level increases in several types of human tumors, and this enzyme participates in the cell cycle process [ 34 – 36 ]. PDK1 phosphorylates the pyruvate dehydrogenase (PDH) E1α subunit to inactivate the PDH enzyme complex, and the PDH enzyme complex can then convert pyruvate into acetyl-CoA.…”