Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of non‑small cell lung cancer

Abstract

The platelet isoform of phosphofructokinase (PFKP) is a rate-limiting enzyme involved in glycolysis that serves an important role in various types of cancer. The aim of the present study was to explore the specific regulatory relationship between PFKP and non-small cell lung cancer (NSCLC) progression. PFKP expression in NSCLC tissues and corresponding adjacent tissues was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analysis. PFKP expression in human bronchial epithelial cells (16HBE) and NSCLC cells (H1299, H23 and A549) was also detected using RT-qPCR. Cell proliferation was detected by Cell Counting Kit-8 and colony formation assays. Transwell invasion and wound healing assays, and flow cytometry were used to detect cell invasion, migration and apoptosis, respectively. The expression levels of glycolysis-associated enzymes (hexokinase-2, lactate dehydrogenase A and glucose transporter-1), epithelial-mesenchymal transition-related proteins (N-cadherin, vimentin and E-cadherin) and apoptosis-related proteins (caspase-3 and B-cell lymphoma-2) were detected by western blotting. Glucose uptake, lactate production and the adenosine trisphosphate/adenosine diphosphate ratio were measured using the corresponding kits. The results of the present study demonstrated that PFKP expression was upregulated in NSCLC tissues and cells, and PFKP expression was related to lymph node metastasis and histological grade. In addition, overexpression of PFKP inhibited cell apoptosis, and promoted proliferation, migration, invasion and glycolysis of H1299 cells, whereas knockdown of PFKP had the opposite effects. In conclusion, PFKP inhibited cell apoptosis, and promoted proliferation, migration, invasion and glycolysis of NSCLC cells; these findings may lay the foundation for novel treatments of NSCLC.

A Lipidated Peptide with Mitochondrial Membrane Localization in Human A549 Lung Cells: From Enhanced Cell-Penetrating Properties to Biological Activity Mechanism

“…It is well documented that HK-II is drastically overexpressed in lung cancer and malignant NSCLC tumor tissues. 49,50 At variance, HK-II is moderately expressed in the adjacent normal tissues. The fact that the expression level of HK-II is significantly higher in the tumor NSCLC tissues, as compared to the normal tissues, designates HK-II as an emerging anticancer therapeutic target.…”

Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer

“…Aerobic glycolysis provides a material basis for growth and proliferation of tumor cells (28), and large amounts of lactic acid cause invasion of tumor tissues to the normal adjacent tissues (29). In non-small cell lung cancer (NSCLC) cell lines, PFKP was revealed to promote proliferation, migration, invasion, epithelial-mesenchymal transition, and glycolysis (30). Furthermore, PFKP mRNA expression was associated with lymph node metastasis in NSCLC tissues (30).…”

Predicting lung adenocarcinoma prognosis with a novel risk scoring based on platelet-related gene expression

“…Studies also have shown that P2RX1 is closely related to the platelet activation pathway [ 27 ]. Phosphofructokinase platelet-type (PFKP) is a rate-limiting enzyme involved in glycolysis and is closely related to the progression of non-small cell lung cancer [ 28 ]. Excised nucleoside triphosphate diphosphate hydrolase (ENTPD) is involved in inflammation and platelet aggregation [ 29 ].…”