Role of PFKFB isoenzymes in cancer stem cells

Cancer stem cells (CSC) are subset of tumor cells with high regenerative ability that are thought to initiate tumor formation; yet constitute a very small part of the existing tumor tissue. This rare cell population shares features with normal stem cells like cell surface markers and pluripotency factors, and can be separated from the rest of the tumor tissue by those features. CSCs shows high resistance to radiotherapy and chemotherapy, and if they could not be destroyed during the treatment process, tumor relapse might occur. There are some studies about energy metabolism gives information about metabolic profile of CSCs in different tissues and tumors. Still, there is no consensus about these metabolic profiles beacuse identification of CSCs differs a lot between different types of tissues and lacks standardization. Fructose 2,6 bisphosphate is an activator of glycolysis specific rate limiting enzyme PFK-1. Its formation and degradation is carried out by 6-phosphofructo-2-kinase / fructose-2,6-bisphosphatase isoenzymes (PFKFB1-4). These isoenzymes expressed in tumor cells at varying levels depending on the tumor type and their expression in CSCs and differentiated tumor cells are dissimilar. In this study, rates of PFKFB isoenzymes and CSC percentage in the cell populations was examined in breast cancer cell line MCF-7 and pancreatic ductal adenocarcinoma cell lines PANC-1 and Mia PaCa-2, to identify a possible correlation. Also, effects of PFKFB suppression on CSC population were examined. Results indicate that expression of PFKFB1 and PFKFB4 isoenzymes increased in the cell groups with high CSC population in PANC-1 and Mia PaCa-2 cell lines, and CSC population decreased in PANC-1 cell line as a result of PFKFB4 suppression. It was found that suppression did not cause any negative effects on the oncogenic potential in all cell lines. According to the data obtained; It is thought that difference in PFKFB4 isoenzyme levels could be a marker of CSCs. Also, PFKFB4 might be selected as a molecular drug target for future studies.