Expression of the v-src or v-fps oncogene increases fructose 2,6-bisphosphate in chick-embryo fibroblasts. Novel mechanism for the stimulation of glycolysis by retroviruses

Abstract

The concentration of fructose 2,6-bisphosphate and the activity of 6-phosphofructo-2-kinase are increased after infection of chick-embryo fibroblasts with the Rous sarcoma virus, or with a temperature-sensitive mutant of this virus at the permissive, but not at the non-permissive, temperature. This is observed after transformation by retroviruses carrying either the v-src or v-fps, but not the v-mil and/or v-myc, oncogenes.Comparison of the effects of the Rous sarcoma virus with those of phorbol myristate acetate on fructose 2,6-bisphosphate suggests that both result from the stimulation of a step which is rate-limiting for 6-phosphofructo-2-kinase activation and which is also controlled by protein kinase C.

An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: Role in tumor cell glycolysis and the Warburg effect

“…F2,6BP is considered to be the most potent stimulator of glycolysis and acts by allosteric activation of PFK-1, which phosphorylates F6P to produce F1,6BP (3,4). PFK-2 catalyzes the synthesis of F2,6BP from F6P, and, in chick-embryo fibroblasts, this catalytic activity has been shown to be increased by oncogenic retroviral transformation (10). Several tissue-specific isoenzymes of PFK-2 have been described, but the isoenzyme that is associated with the enhanced glycolysis of tumor cells has not been identified previously (4).…”

“…Multiple established cancer cell lines (i.e., Ehrlich ascites tumor cells, HeLa cells, HT29 colon adenocarcinoma cells, and Lewis lung carcinoma cells) have markedly elevated levels of F2,6BP when compared with normal tissue cells (6)(7)(8)(9). Transformation of chick-embryo fibroblasts by retroviruses carrying either the v-src or v-fps oncogenes has been observed to induce F2,6BP synthesis and to cause increased glycolytic flux and cell proliferation (10). These data suggest that activation and͞or over-expression of PFK-2-catalyzed F2,6BP synthesis may contribute to transformation and cancer cell proliferation (4,5).…”

Effects of overexpression of the liver subunit of 6-phosphofructo-1-kinase on the metabolism of a cultured mammalian cell line

“…There is also, in tumours, a correlation between the high glycolytic flux maintained by these tissues and the activity of the liver isoform of PFK-1 (PFK-L) [3]. Furthermore, the level of fructose 2,6-bisphosphate in tumour cells is often increased, and transformation of cells with retroviruses containing either the v-src or v-fps oncogene has been shown to increase both the fructose 2,6-bisphosphate concentration and glycolytic flux [4,5]. However, although it is clear that the enzyme is tightly regulated and that there is a correlation between its activity and glycolytic flux, the evidence that it is rate-limiting for glycolytic flux is very poor.…”

Glucose decreases respiratory control ratio in EL‐4 tumor cells

“…Several mechanisms for such energy metabolism have been suggested, e.g. small mitochondria content and their abnormal structure [1,2], elevated ATPases activities [3,4]° high hexo~ kinase activity and its association with mitochondrial outer membrane [5], increased level of frttetose-2,6-diphosphate, a glycolysis activator [6]. However, the contribution of the proposed mechanisms in the bioenergeties of tumor cells has not been fully evaluated.…”