PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells
| Autor: | Ahmet Akkoç, Selahattin C. Ozcan, Sabire Guler, Saime Güzel, Robertino J. Muchut, Yunus Gurpinar, Tugba H. Altunok, Abdullah Yalcin, Aybike Sarioglu, Alberto A. Iglesias, Yoannis Imbert-Fernandez, Amy L. Clem, Jason Chesney |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cytoplasm Phosphofructokinase-2 Glucose uptake RNA Splicing Clinical Biochemistry Pentose phosphate pathway Adenocarcinoma Isozyme Gene Expression Regulation Enzymologic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pancreatic cancer Cell Line Tumor medicine Humans Glycolysis Gene Silencing RNA Messenger Molecular Biology Pancreas Cell Proliferation Cell Nucleus Chemistry Cell growth Cell Differentiation Cell Biology General Medicine PFKFB4 medicine.disease Cell biology Gene Expression Regulation Neoplastic Isoenzymes Pancreatic Neoplasms 030104 developmental biology Phenotype Fructose 2 6-bisphosphate 030220 oncology & carcinogenesis HeLa Cells |
| Zdroj: | Molecular and cellular biochemistry. 470(1-2) |
| ISSN: | 1573-4919 |
| Popis: | Tumor cells increase glucose metabolism through glycolysis and pentose phosphate pathways to meet the bioenergetic and biosynthetic demands of rapid cell proliferation. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) are key regulators of glucose metabolism via their synthesis of fructose-2,6-bisphosphate (F2,6BP), a potent activator of glycolysis. Previous studies have reported the co-expression of PFKFB isozymes, as well as the mRNA splice variants of particular PFKFB isozymes, suggesting non-redundant functions. Majority of the evidence demonstrating a requirement for PFKFB activity in increased glycolysis and oncogenic properties in tumor cells comes from studies on PFKFB3 and PFKFB4 isozymes. In this study, we show that the PFKFB2 isozyme is expressed in tumor cell lines of various origin, overexpressed and localizes to the nucleus in pancreatic adenocarcinoma, relative to normal pancreatic tissue. We then demonstrate the differential intracellular localization of two PFKFB2 mRNA splice variants and that, when ectopically expressed, cytoplasmically localized mRNA splice variant causes a greater increase in F2,6BP which coincides with an increased glucose uptake, as compared with the mRNA splice variant localizing to the nucleus. We then show that PFKFB2 expression is required for steady-state F2,6BP levels, glycolytic activity, and proliferation of pancreatic adenocarcinoma cells. In conclusion, this study may provide a rationale for detailed investigation of PFKFB2's requirement for the glycolytic and oncogenic phenotype of pancreatic adenocarcinoma cells. |
| Databáze: | OpenAIRE |
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