Differential expression of phosphofructokinase-1 isoforms correlates with the glycolytic efficiency of breast cancer cells.
Cancer cells are characterized by increased aerobic glycolysis, which correlates with a negative prognosis. Although this correlation is well known, the mechanism of the elevated rate of glycolysis in cancer and the role of glycolytic enzymes have yet to be determined. The present work aims to evaluate the activity of the major enzymes that regulate glycolysis in breast cancer cell lines of varying aggressiveness. MCF10A, MCF-7 and MDA-mb-231 are human breast-derived cell lines with non-tumorigenic, tumorigenic and metastatic profiles, respectively. These cell lines have increasing degrees of glycolytic efficiency, i.e., lactate produced per glucose consumed, corresponding to their metastatic potential. Although, there are no differences in phosphofructokinase (PFK) or pyruvate kinase (PK) activities, the activity of hexokinase (HK) activity is higher in both tumorigenic cell lines compared to MCF10A cells. No difference in HK activity is observed between MCF-7 and MDA-mb-231 cells, suggesting that the difference in their glycolytic efficiency could not be attributed to this enzyme. However, we find that expression of the PFK-L isoform directly and strongly correlates with aggressiveness and glycolytic efficiency in these cell lines. Thus, we conclude that glycolytic efficiency, which is important for the survival of cancer cells, depends primarily on the preferential expression of PFK-L over the M and P isoforms.
Zancan
Patricia
P
Laboratório de Oncobiologia Molecular - LabOMol, Faculdade de Farmácia, UFRJ, Brazil. pzancan@ufrj.br
Sola-Penna
Mauro
M
Furtado
Cristiane Marques
CM
Da Silva
Daniel
D
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D055442:Metabolome / Q000235:genetics; D010732:Phosphofructokinase-1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007527:Isoenzymes; D012333:RNA, Messenger; D010732:Phosphofructokinase-1