Artículo
PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells
Ozcan, Selahattin C.; Sarioglu, Aybike; Altunok, Tugba H.; Akkoc, Ahmet; Guzel, Saime; Guler, Sabire; Imbert-Fernandez, Yoannis; Muchut, Robertino José
; Iglesias, Alberto Alvaro
; Gurpinar, Yunus; Clem, Amy L.; Chesney, Jason A.; Yalcin, Abdullah
![Icon](/themes/CONICETDigital/images/conicet.png)
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
05/2020
Editorial:
Springer
Revista:
Molecular and Cellular Biochemistry
ISSN:
0300-8177
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
FRUCTOSE-2,6-BISPHOSPHATE
,
GLYCOLYSIS
,
PANCREATIC ADENOCARCINOMA
,
PFKFB2
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - SANTA FE)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Articulos(IAL)
Articulos de INSTITUTO DE AGROBIOTECNOLOGIA DEL LITORAL
Articulos de INSTITUTO DE AGROBIOTECNOLOGIA DEL LITORAL
Citación
Ozcan, Selahattin C.; Sarioglu, Aybike; Altunok, Tugba H.; Akkoc, Ahmet; Guzel, Saime; et al.; PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells; Springer; Molecular and Cellular Biochemistry; 470; 1-2; 5-2020; 115-129
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